rs6039

Variant names:

Variant summary

Our verdict is The variant received -16 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Strong

The NM_019616.4(F7):c.64+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.128 (AC=202,310) in the gnomAD database across 1,577,850 control chromosomes, including 15,697 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.273. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2371 hom., cov: 30)

Exomes 𝑓: 0.12 ( 13326 hom. )

Consequence

F7
NM_019616.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.999

Publications

16 publications found

Variant links:

Genes affected

F7 (HGNC:3544): (coagulation factor VII) This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

F7 Gene-Disease associations (from GenCC):

congenital factor VII deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet
factor VII deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

F7 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_019616.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -16 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2725 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_019616.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F7	NM_019616.4	MANE Select	c.64+9G>A	intron	N/A	NP_062562.1	P08709-2
F7	NM_000131.5		c.64+9G>A	intron	N/A	NP_000122.1	P08709-1
F7	NM_001267554.2		c.64+9G>A	intron	N/A	NP_001254483.1	F5H8B0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F7	ENST00000346342.8	TSL:1 MANE Select	c.64+9G>A	intron	N/A	ENSP00000329546.4	P08709-2
F7	ENST00000375581.3	TSL:1	c.64+9G>A	intron	N/A	ENSP00000364731.3	P08709-1
F7	ENST00000891255.1		c.64+9G>A	intron	N/A	ENSP00000561314.1	A0ACI8QDK7

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24363

AN:

151592

Hom.:

2367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.0326

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.175

GnomAD2 exomes

AF:

0.139

AC:

27826

AN:

200172

AF XY:

0.145

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.0349

Gnomad FIN exome

AF:

0.0674

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.125

AC:

177914

AN:

1426140

Hom.:

13326

Cov.:

AF XY:

0.130

AC XY:

91377

AN XY:

705306

show subpopulations

African (AFR)

AF:

0.277

AC:

9204

AN:

33194

American (AMR)

AF:

0.123

AC:

4883

AN:

39754

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4618

AN:

25336

East Asian (EAS)

AF:

0.0406

AC:

1575

AN:

38758

South Asian (SAS)

AF:

0.273

AC:

22219

AN:

81298

European-Finnish (FIN)

AF:

0.0711

AC:

3505

AN:

49288

Middle Eastern (MID)

AF:

0.231

AC:

1316

AN:

5704

European-Non Finnish (NFE)

AF:

0.112

AC:

122365

AN:

1093738

Other (OTH)

AF:

0.139

AC:

8229

AN:

59070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6894

13788

20681

27575

34469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4628

9256

13884

18512

23140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.161

AC:

24396

AN:

151710

Hom.:

2371

Cov.:

AF XY:

0.160

AC XY:

11873

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.265

AC:

10931

AN:

41302

American (AMR)

AF:

0.137

AC:

2086

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3460

East Asian (EAS)

AF:

0.0327

AC:

167

AN:

5112

South Asian (SAS)

AF:

0.270

AC:

1285

AN:

4768

European-Finnish (FIN)

AF:

0.0688

AC:

728

AN:

10574

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7942

AN:

67920

Other (OTH)

AF:

0.174

AC:

364

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

951

1903

2854

3806

4757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.167

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.172

AC:

18067

AN:

105292

Hom.:

1827

Local populations

ABraOM SABE-WGS-1171

AF:

0.184

AC:

430

AN:

2342

Hom.:

ChinaMAP Phase 1

AF:

0.0380

Denmark Genome

AF:

0.0933

AC:

AN:

300

ESP6500 (Exome Variant Server)

AF:

0.163

AC:

2105

AN:

12928

show subpopulations

European American

AF:

0.113

AC:

970

AN:

8568

African American

AF:

0.260

AC:

1135

AN:

4360

GenomeAsia100K

AF:

0.158

AC:

549

AN:

3478

show subpopulations

Oceania

AF:

0.0541

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.0570

AC:

AN:

702

Hom.:

South-East Asia

AF:

0.0549

AC:

AN:

692

Hom.:

South Asia

AF:

0.256

AC:

370

AN:

1448

Hom.:

Africa

AF:

0.274

AC:

AN:

208

Hom.:

America

AF:

0.0385

AC:

AN:

Hom.:

West Eurasia

AF:

0.149

AC:

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.0300

AC:

216

AN:

7234

Qatari Genome

AF:

0.199

AC:

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0427

AC:

5226

AN:

122298

Hom.:

143

Turkish Variome

AF:

0.198

AC:

1301

AN:

6558

Hom.:

137

UK10K

AF:

0.116

AC:

880

AN:

7562

show subpopulations

TwinsUK

AF:

0.126

AC:

449

AN:

3574

ALSPAC

AF:

0.108

AC:

415

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0387

AC:

347

AN:

8960

Hom.:

Case/control cohorts

Cohort

Cases

Controls

BipEx

(Bipolar disorder (including schizoaffective))

3213 / 28278AF: 0.113622

3291 / 28780AF: 0.114350

SCHEMA

(Schizophrenia)

21673 / 121586AF: 0.178252

38110 / 206742AF: 0.184336

Allele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Factor VII deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.4

(source)

DANN

Benign

0.44

PhyloP100

-1.0

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.0

AlphaGenome AVI

Benign

1.2

(source)

GPN-Star LLR

-1.3

(source)

GPN-Star score

1.3

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Pangolin (max)

Benign

0.020

(source)

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

Case/control cohorts

ClinVar

Computational scores

Splicing

Publications

Other links and lift over