6-105100975-C-T

Position:

• chr6-105100975-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001199563.2(BVES):​c.*114G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 1,265,296 control chromosomes in the GnomAD database, including 578,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70836 hom., cov: 31)
  • Exomes 𝑓: 0.95 (507394 hom.)
• Consequence: BVES NM_001199563.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-105100975-C-T is Benign according to our data. Variant chr6-105100975-C-T is described in ClinVar as [Benign]. Clinvar id is 1192585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BVES	NM_001199563.2	c.*114G>A		3_prime_UTR_variant	8/8	ENST00000314641.10	NP_001186492.1
BVES	NM_007073.4	c.*114G>A		3_prime_UTR_variant	8/8		NP_009004.2
BVES	NM_147147.4	c.*114G>A		3_prime_UTR_variant	8/8		NP_671488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BVES	ENST00000314641	c.*114G>A		3_prime_UTR_variant	8/8	1	NM_001199563.2	ENSP00000313172.5
BVES	ENST00000336775	c.*114G>A		3_prime_UTR_variant	8/8	1		ENSP00000337259.5
BVES	ENST00000446408	c.*114G>A		3_prime_UTR_variant	8/8	1		ENSP00000397310.2

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146730 AN: 152136 Hom.: 70775 Cov.: 31

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.958

GnomAD4 exome AF: 0.955 AC: 1062597 AN: 1113042 Hom.: 507394 Cov.: 14 AF XY: 0.954 AC XY: 524402 AN XY: 549880

Gnomad4 AFR exome AF: 0.993

Gnomad4 AMR exome AF: 0.979

Gnomad4 ASJ exome AF: 0.934

Gnomad4 EAS exome AF: 0.927

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.945

Gnomad4 NFE exome AF: 0.957

Gnomad4 OTH exome AF: 0.951

GnomAD4 genome AF: 0.965 AC: 146851 AN: 152254 Hom.: 70836 Cov.: 31 AF XY: 0.963 AC XY: 71675 AN XY: 74456

Gnomad4 AFR AF: 0.992

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.957

Gnomad4 OTH AF: 0.958

Alfa AF: 0.957 Hom.: 77852

Bravo AF: 0.967

Asia WGS AF: 0.931 AC: 3239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Autosomal recessive limb-girdle muscular dystrophy type 2X Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs221657; hg19: chr6-105548850; COSMIC: COSV58949872;