Genetic Variant TRPV6:c.*5G>A (chr7-142871702-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018646.6(TRPV6):c.*5G>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 0.000777 in 1,576,256 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0042 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 6 hom. )

Consequence

TRPV6
NM_018646.6 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.76

Variant links:

Genes affected

TRPV6 (HGNC:14006): (transient receptor potential cation channel subfamily V member 6) This gene encodes a member of a family of multipass membrane proteins that functions as calcium channels. The encoded protein contains N-terminal ankyrin repeats, which are required for channel assembly and regulation. Translation initiation for this protein occurs at a non-AUG start codon that is decoded as methionine. This gene is situated next to a closely related gene for transient receptor potential cation channel subfamily V member 5 (TRPV5). This locus has experienced positive selection in non-African populations, resulting in several non-synonymous codon differences among individuals of different genetic backgrounds. [provided by RefSeq, Feb 2015]

TRPV6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-142871702-C-T is Benign according to our data. Variant chr7-142871702-C-T is described in ClinVar as [Benign]. Clinvar id is 3052361.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00418 (636/152288) while in subpopulation AFR AF= 0.0146 (608/41542). AF 95% confidence interval is 0.0137. There are 11 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV6	NM_018646.6 link	c.*5G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000359396.9	NP_061116.5	Q9H1D0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV6	ENST00000359396 link	c.*5G>A	3_prime_UTR_variant	Exon 15 of 15	1	NM_018646.6	ENSP00000352358.5	Q9H1D0-1A0A1X7SBT1
TRPV6	ENST00000485138.5 link	n.1913G>A	non_coding_transcript_exon_variant	Exon 9 of 9	2
TRPV6	ENST00000615386.4 link	n.9944G>A	non_coding_transcript_exon_variant	Exon 12 of 12	2

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

636

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00108

AC:

246

AN:

228174

Hom.:

AF XY:

0.000764

AC XY:

AN XY:

122990

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000495

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.000413

AC:

588

AN:

1423968

Hom.:

Cov.:

AF XY:

0.000347

AC XY:

244

AN XY:

703784

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.000398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000156

Gnomad4 OTH exome

AF:

0.000801

GnomAD4 genome

AF:

0.00418

AC:

636

AN:

152288

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00501

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRPV6-related disorder

Benign:1

Oct 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

DANN

Benign

0.65

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