Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_019616.4(F7):c.740-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,586,184 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0054 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 77 hom. )

Consequence

F7
NM_019616.4 intron

Scores

Splicing: ADA: 0.0001635

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.144

Publications

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

F7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-113118403-T-C is Benign according to our data. Variant chr13-113118403-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 255220.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00538 (819/152330) while in subpopulation NFE AF = 0.00904 (615/68024). AF 95% confidence interval is 0.00845. There are 3 homozygotes in GnomAd4. There are 372 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
F7	NM_019616.4	MANE Select	c.740-10T>C	intron	N/A	NP_062562.1
F7	NM_000131.5		c.806-10T>C	intron	N/A	NP_000122.1
F7	NM_001267554.2		c.554-10T>C	intron	N/A	NP_001254483.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
F7	ENST00000346342.8	TSL:1 MANE Select	c.740-10T>C	intron	N/A	ENSP00000329546.4
F7	ENST00000375581.3	TSL:1	c.806-10T>C	intron	N/A	ENSP00000364731.3
F7	ENST00000541084.5	TSL:2	c.554-10T>C	intron	N/A	ENSP00000442051.2

Frequencies

GnomAD3 genomes

AF:

0.00538

AC:

819

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00763

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00904

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00495

AC:

1155

AN:

233218

AF XY:

0.00500

show subpopulations

Gnomad AFR exome

AF:

0.00177

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.000110

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00802

Gnomad NFE exome

AF:

0.00866

Gnomad OTH exome

AF:

0.00445

GnomAD4 exome

AF:

0.00836

AC:

11989

AN:

1433854

Hom.:

Cov.:

AF XY:

0.00811

AC XY:

5758

AN XY:

710084

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33202

American (AMR)

AF:

0.00159

AC:

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.0000791

AC:

AN:

25270

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39274

South Asian (SAS)

AF:

0.000497

AC:

AN:

84444

European-Finnish (FIN)

AF:

0.00766

AC:

335

AN:

43710

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0102

AC:

11168

AN:

1098798

Other (OTH)

AF:

0.00553

AC:

328

AN:

59336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

714

1428

2141

2855

3569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.00538

AC:

819

AN:

152330

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

372

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41580

American (AMR)

AF:

0.00268

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00763

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00904

AC:

615

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00431

Hom.:

Bravo

AF:

0.00477

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Factor VII deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.28

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs3093266

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over