6-105115802-A-G

Position:

chr6-105115802-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001199563.2(BVES):c.842T>C(p.Leu281Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0107 in 1,613,760 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 11 hom., cov: 33)

Exomes 𝑓: 0.011 ( 133 hom. )

Consequence

BVES
NM_001199563.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.47

Variant links:

Genes affected

BVES (HGNC:1152): (blood vessel epicardial substance) This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in development of these tissues. The mouse ortholog may be involved in the regeneration of adult skeletal muscle and may act as a cell adhesion molecule in coronary vasculogenesis. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

BVES 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 (MetaRNN=0.0050093234).

BP6

Variant 6-105115802-A-G is Benign according to our data. Variant chr6-105115802-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1196394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00957 (1458/152284) while in subpopulation NFE AF= 0.0117 (799/68026). AF 95% confidence interval is 0.0111. There are 11 homozygotes in gnomad4. There are 755 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BVES	NM_001199563.2 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/8	ENST00000314641.10	NP_001186492.1	Q8NE79
BVES	NM_007073.4 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/8		NP_009004.2	Q8NE79
BVES	NM_147147.4 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/8		NP_671488.1	Q8NE79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BVES	ENST00000314641.10 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/8	1	NM_001199563.2	ENSP00000313172.5	Q8NE79
BVES	ENST00000336775.9 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/8	1		ENSP00000337259.5	Q8NE79
BVES	ENST00000446408.2 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/8	1		ENSP00000397310.2	Q8NE79

Frequencies

GnomAD3 genomes

AF:

0.00958

AC:

1458

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0107

AC:

2690

AN:

251104

Hom.:

AF XY:

0.0111

AC XY:

1505

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00443

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00688

Gnomad FIN exome

AF:

0.0402

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0109

AC:

15861

AN:

1461476

Hom.:

133

Cov.:

AF XY:

0.0107

AC XY:

7750

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00479

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00613

Gnomad4 FIN exome

AF:

0.0373

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00942

GnomAD4 genome

AF:

0.00957

AC:

1458

AN:

152284

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

755

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0405

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00740

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0103

AC:

ExAC

AF:

0.0103

AC:

1250

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.0106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	BVES: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 22, 2020	- -

BVES-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.036

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

.;.;T

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.28

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.81

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.040

D;D;D

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.28

MPC

0.38

ClinPred

0.037

GERP RS

3.6

Varity_R

0.13

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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