Genetic Variant F7:p.His153His (chr13-113115754-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019616.4(F7):c.459C>T(p.His153His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,076 control chromosomes in the GnomAD database, including 14,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1330 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13296 hom. )

Consequence

F7
NM_019616.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.13

Publications

25 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), Ambry Genetics, Orphanet, 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 -21 ACMG points.

BP4

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

BP6

Variant 13-113115754-C-T is Benign according to our data. Variant chr13-113115754-C-T is described in ClinVar as Benign. ClinVar VariationId is 255218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
F7	NM_019616.4	MANE Select	c.459C>T	p.His153His	synonymous	Exon 5 of 8	NP_062562.1	P08709-2
F7	NM_000131.5		c.525C>T	p.His175His	synonymous	Exon 6 of 9	NP_000122.1
F7	NM_001267554.2		c.273C>T	p.His91His	synonymous	Exon 3 of 6	NP_001254483.1	F5H8B0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F7	ENST00000346342.8	TSL:1 MANE Select	c.459C>T	p.His153His	synonymous	Exon 5 of 8	ENSP00000329546.4	P08709-2
F7	ENST00000375581.3	TSL:1	c.525C>T	p.His175His	synonymous	Exon 6 of 9	ENSP00000364731.3	P08709-1
F7	ENST00000891255.1		c.672C>T	p.His224His	synonymous	Exon 6 of 9	ENSP00000561314.1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19248

AN:

152142

Hom.:

1328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.0765

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.144

GnomAD2 exomes

AF:

0.137

AC:

34334

AN:

250174

AF XY:

0.146

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.0502

Gnomad FIN exome

AF:

0.0749

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.126

AC:

183916

AN:

1460816

Hom.:

13296

Cov.:

AF XY:

0.132

AC XY:

95567

AN XY:

726700

show subpopulations

African (AFR)

AF:

0.138

AC:

4627

AN:

33478

American (AMR)

AF:

0.118

AC:

5269

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5104

AN:

26136

East Asian (EAS)

AF:

0.0580

AC:

2304

AN:

39700

South Asian (SAS)

AF:

0.278

AC:

23941

AN:

86248

European-Finnish (FIN)

AF:

0.0786

AC:

4125

AN:

52456

Middle Eastern (MID)

AF:

0.221

AC:

1274

AN:

5768

European-Non Finnish (NFE)

AF:

0.116

AC:

129202

AN:

1111942

Other (OTH)

AF:

0.134

AC:

8070

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9524

19048

28573

38097

47621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4740

9480

14220

18960

23700

<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:

0.126

AC:

19256

AN:

152260

Hom.:

1330

Cov.:

AF XY:

0.126

AC XY:

9374

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.134

AC:

5581

AN:

41552

American (AMR)

AF:

0.122

AC:

1871

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

720

AN:

3472

East Asian (EAS)

AF:

0.0473

AC:

245

AN:

5184

South Asian (SAS)

AF:

0.276

AC:

1331

AN:

4820

European-Finnish (FIN)

AF:

0.0765

AC:

811

AN:

10600

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.120

AC:

8177

AN:

68016

Other (OTH)

AF:

0.143

AC:

302

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

888

1777

2665

3554

4442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.128

Hom.:

2567

Bravo

AF:

0.129

Asia WGS

AF:

0.159

AC:

552

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.137

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Factor VII deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

(source)

DANN

Benign

0.63

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over