6-105100845-A-T

Position:

• chr6-105100845-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001199563.2(BVES):​c.*244T>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 0.00911 in 297,920 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 31)
  • Exomes 𝑓: 0.0056 (6 hom.)
• Consequence: BVES NM_001199563.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.809

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=-0.91).
• BP6: Variant 6-105100845-A-T is Benign according to our data. Variant chr6-105100845-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1896/152308) while in subpopulation AFR AF= 0.03 (1249/41572). AF 95% confidence interval is 0.0287. There are 20 homozygotes in gnomad4. There are 989 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BVES	NM_001199563.2	c.*244T>A		3_prime_UTR_variant	8/8	ENST00000314641.10	NP_001186492.1
BVES	NM_007073.4	c.*244T>A		3_prime_UTR_variant	8/8		NP_009004.2
BVES	NM_147147.4	c.*244T>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.*244T>A		3_prime_UTR_variant	8/8	1	NM_001199563.2	ENSP00000313172.5
BVES	ENST00000336775	c.*244T>A		3_prime_UTR_variant	8/8	1		ENSP00000337259.5
BVES	ENST00000446408	c.*244T>A		3_prime_UTR_variant	8/8	1		ENSP00000397310.2

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1900 AN: 152190 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00447

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00562 AC: 818 AN: 145612 Hom.: 6 Cov.: 3 AF XY: 0.00568 AC XY: 423 AN XY: 74524

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.00484

Gnomad4 ASJ exome AF: 0.000691

Gnomad4 EAS exome AF: 0.000170

Gnomad4 SAS exome AF: 0.00134

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.00479

Gnomad4 OTH exome AF: 0.00650

GnomAD4 genome AF: 0.0124 AC: 1896 AN: 152308 Hom.: 20 Cov.: 31 AF XY: 0.0133 AC XY: 989 AN XY: 74460

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.00447

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00183 Hom.: 0

Bravo AF: 0.0126

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs17065481; hg19: chr6-105548720;