7-142925619-A-G

Position:

• chr7-142925619-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019841.7(TRPV5):​c.1032T>C​(p.Thr344Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 1,614,014 control chromosomes in the GnomAD database, including 646,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (49474 hom., cov: 32)
  • Exomes 𝑓: 0.90 (596881 hom.)
• Consequence: TRPV5 NM_019841.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.170

Genes affected

TRPV5 (HGNC:3145): (transient receptor potential cation channel subfamily V member 5) This gene is a member of the transient receptor family and the TrpV subfamily. The calcium-selective channel encoded by this gene has 6 transmembrane-spanning domains, multiple potential phosphorylation sites, an N-linked glycosylation site, and 5 ANK repeats. This protein forms homotetramers or heterotetramers and is activated by a low internal calcium level. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-142925619-A-G is Benign according to our data. Variant chr7-142925619-A-G is described in ClinVar as [Benign]. Clinvar id is 768211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV5	NM_019841.7	c.1032T>C	p.Thr344Thr	synonymous_variant	8/15	ENST00000265310.6	NP_062815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV5	ENST00000265310.6	c.1032T>C	p.Thr344Thr	synonymous_variant	8/15	1	NM_019841.7	ENSP00000265310.1
TRPV5	ENST00000442623.1	c.1032T>C	p.Thr344Thr	synonymous_variant	8/8	1		ENSP00000406572.1
TRPV5	ENST00000439304.5	c.867T>C	p.Thr289Thr	synonymous_variant	7/14	5		ENSP00000406361.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118636 AN: 152014 Hom.: 49455 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.801

GnomAD4 exome AF: 0.900 AC: 1316405 AN: 1461882 Hom.: 596881 Cov.: 79 AF XY: 0.901 AC XY: 655204 AN XY: 727236

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.895

Gnomad4 EAS exome AF: 0.974

Gnomad4 SAS exome AF: 0.867

Gnomad4 FIN exome AF: 0.890

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.878

GnomAD4 genome AF: 0.780 AC: 118700 AN: 152132 Hom.: 49474 Cov.: 32 AF XY: 0.785 AC XY: 58358 AN XY: 74362

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.804

Alfa AF: 0.891 Hom.: 94582

Bravo AF: 0.765

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4252435; hg19: chr7-142622714;