NM_019616.4:c.64+4C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_019616.4(F7):c.64+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,583,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

F7
NM_019616.4 splice_region, intron

Scores

Splicing: ADA: 0.00008416

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: -0.542

Publications

0 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 13-113105909-C-T is Benign according to our data. Variant chr13-113105909-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 517720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00168 (256/152062) while in subpopulation AFR AF = 0.00571 (237/41476). AF 95% confidence interval is 0.00512. There are 1 homozygotes in GnomAd4. There are 124 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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	UniProt
F7	NM_019616.4	MANE Select	c.64+4C>T	splice_region intron	N/A	NP_062562.1	P08709-2
F7	NM_000131.5		c.64+4C>T	splice_region intron	N/A	NP_000122.1
F7	NM_001267554.2		c.64+4C>T	splice_region 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+4C>T	splice_region intron	N/A	ENSP00000329546.4	P08709-2
F7	ENST00000375581.3	TSL:1	c.64+4C>T	splice_region intron	N/A	ENSP00000364731.3	P08709-1
F7	ENST00000891255.1		c.64+4C>T	splice_region intron	N/A	ENSP00000561314.1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.000288

AC:

AN:

204834

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.00385

Gnomad AMR exome

AF:

0.000137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000190

Gnomad FIN exome

AF:

0.000115

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

194

AN:

1431030

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

708142

show subpopulations

African (AFR)

AF:

0.00388

AC:

129

AN:

33272

American (AMR)

AF:

0.000248

AC:

AN:

40356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25386

East Asian (EAS)

AF:

0.000129

AC:

AN:

38904

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81604

European-Finnish (FIN)

AF:

0.000121

AC:

AN:

49752

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.0000210

AC:

AN:

1096770

Other (OTH)

AF:

0.000321

AC:

AN:

59276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00168

AC:

256

AN:

152062

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00571

AC:

237

AN:

41476

American (AMR)

AF:

0.00111

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67990

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000792

Hom.:

Bravo

AF:

0.00179

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital factor VII deficiency (1)

Congenital factor VII deficiency;C1832662:Myocardial infarction, susceptibility to (1)

Factor VII deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.4

(source)

DANN

Benign

0.69

PhyloP100

-0.54

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.0

Mutation Taster

=8/92

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000084

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.12

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.

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

Computational scores

Splicing

Publications

Other links and lift over