rs6041

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019616.4(F7):c.740-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,579,270 control chromosomes in the GnomAD database, including 12,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1211 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11503 hom. )

Consequence

F7
NM_019616.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.77

Publications

22 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 13-113118393-G-A is Benign according to our data. Variant chr13-113118393-G-A is described in ClinVar as Benign. ClinVar VariationId is 255221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F7	NM_019616.4 link	c.740-20G>A		intron_variant	Intron 7 of 7	ENST00000346342.8	NP_062562.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
F7	ENST00000346342.8 link	c.740-20G>A	intron_variant	Intron 7 of 7	1	NM_019616.4	ENSP00000329546.4
F7	ENST00000375581.3 link	c.806-20G>A	intron_variant	Intron 8 of 8	1		ENSP00000364731.3
F7	ENST00000541084.5 link	c.554-20G>A	intron_variant	Intron 5 of 5	2		ENSP00000442051.2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17979

AN:

152092

Hom.:

1203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0474

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.0696

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.130

AC:

29605

AN:

227000

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.0503

Gnomad FIN exome

AF:

0.0718

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.117

AC:

166410

AN:

1427060

Hom.:

11503

Cov.:

AF XY:

0.122

AC XY:

86367

AN XY:

705972

show subpopulations

African (AFR)

AF:

0.130

AC:

4323

AN:

33142

American (AMR)

AF:

0.108

AC:

4730

AN:

43922

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4725

AN:

24746

East Asian (EAS)

AF:

0.0600

AC:

2355

AN:

39250

South Asian (SAS)

AF:

0.277

AC:

23041

AN:

83196

European-Finnish (FIN)

AF:

0.0747

AC:

3148

AN:

42132

Middle Eastern (MID)

AF:

0.212

AC:

1204

AN:

5666

European-Non Finnish (NFE)

AF:

0.105

AC:

115525

AN:

1095848

Other (OTH)

AF:

0.124

AC:

7359

AN:

59158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8517

17035

25552

34070

42587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4356

8712

13068

17424

21780

<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:

0.118

AC:

18009

AN:

152210

Hom.:

1211

Cov.:

AF XY:

0.119

AC XY:

8822

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.128

AC:

5326

AN:

41532

American (AMR)

AF:

0.117

AC:

1783

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3464

East Asian (EAS)

AF:

0.0475

AC:

245

AN:

5162

South Asian (SAS)

AF:

0.274

AC:

1324

AN:

4826

European-Finnish (FIN)

AF:

0.0696

AC:

739

AN:

10612

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7388

AN:

67996

Other (OTH)

AF:

0.134

AC:

284

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

838

1676

2515

3353

4191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.112

Hom.:

1851

Bravo

AF:

0.121

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.8

(source)

DANN

Benign

0.80

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over