7-142882184-T-C

Position:

• chr7-142882184-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018646.6(TRPV6):​c.248+3205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,368 control chromosomes in the GnomAD database, including 6,364 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (6362 hom., cov: 32)
  • Exomes 𝑓: 0.093 (2 hom.)
• Consequence: TRPV6 NM_018646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV6	NM_018646.6	c.248+3205A>G		intron_variant		ENST00000359396.9	NP_061116.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV6	ENST00000359396.9	c.248+3205A>G		intron_variant		1	NM_018646.6	ENSP00000352358.5
TRPV6	ENST00000436401.1	c.-68+3463A>G		intron_variant		4		ENSP00000411100.1
TRPV6	ENST00000615386.4	n.3206A>G		non_coding_transcript_exon_variant	1/12	2
ENSG00000224970	ENST00000438839.2	n.99+6250T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30428 AN: 152004 Hom.: 6342 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.0935 AC: 23 AN: 246 Hom.: 2 Cov.: 0 AF XY: 0.0811 AC XY: 12 AN XY: 148

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0294

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.200 AC: 30491 AN: 152122 Hom.: 6362 Cov.: 32 AF XY: 0.192 AC XY: 14319 AN XY: 74402

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0729

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.177

Alfa AF: 0.152 Hom.: 780

Bravo AF: 0.219

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.40

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: rs4987622; hg19: chr7-142579929;