1-169560735-C-T

Position:

chr1-169560735-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000130.5(F5):c.405G>A(p.Ala135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,612,154 control chromosomes in the GnomAD database, including 45,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8966 hom., cov: 31)

Exomes 𝑓: 0.20 ( 36085 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.79

Variant links:

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

F5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-169560735-C-T is Benign according to our data. Variant chr1-169560735-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169560735-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5 linkuse as main transcript	c.405G>A	p.Ala135=	synonymous_variant	4/25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.405G>A	p.Ala135=	synonymous_variant	4/25	1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3 linkuse as main transcript	c.405G>A	p.Ala135=	synonymous_variant	4/25	5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46101

AN:

151608

Hom.:

8956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.0879

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.285

GnomAD3 exomes

AF:

0.257

AC:

64502

AN:

251236

Hom.:

11156

AF XY:

0.245

AC XY:

33228

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.679

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.200

AC:

292195

AN:

1460430

Hom.:

36085

Cov.:

AF XY:

0.198

AC XY:

143756

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.530

Gnomad4 AMR exome

AF:

0.271

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.304

AC:

46142

AN:

151724

Hom.:

8966

Cov.:

AF XY:

0.306

AC XY:

22699

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.651

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.288

Alfa

AF:

0.209

Hom.:

7996

Bravo

AF:

0.319

Asia WGS

AF:

0.447

AC:

1554

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.175

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombophilia due to activated protein C resistance

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital factor V deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Budd-Chiari syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Factor V deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Thrombophilia due to thrombin defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.42

Position offset: -2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over