Variant chr1-169512493-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000130.5(F5):c.*1820A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,132 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 348 hom., cov: 32)

Consequence

F5
NM_000130.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0810

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-169512493-T-G is Benign according to our data. Variant chr1-169512493-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 293544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5 linkuse as main transcript	c.*1820A>C		3_prime_UTR_variant	25/25	ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.*1820A>C		3_prime_UTR_variant	25/25	1	NM_000130.5	P2

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8416

AN:

152014

Hom.:

347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0751

Gnomad EAS

AF:

0.0295

Gnomad SAS

AF:

0.0656

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0647

Gnomad OTH

AF:

0.0641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0554

AC:

8425

AN:

152132

Hom.:

348

Cov.:

AF XY:

0.0577

AC XY:

4293

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.0751

Gnomad4 EAS

AF:

0.0296

Gnomad4 SAS

AF:

0.0654

Gnomad4 FIN

AF:

0.0853

Gnomad4 NFE

AF:

0.0648

Gnomad4 OTH

AF:

0.0634

Alfa

AF:

0.0614

Hom.:

Bravo

AF:

0.0517

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

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	- -

Budd-Chiari syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Thrombophilia due to thrombin defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

DANN

Benign

0.54

Splicing

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