rs4987622

Variant names:

• chr7-142882184-T-C
• rs4987622
• NM_018646.6:c.248+3205A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• hyperparathyroidism, transient neonatal

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P
• intestinal hypomagnesemia 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pancreatitis

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• neonatal severe primary hyperparathyroidism

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000224970 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018646.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV6	NM_018646.6	MANE Select	c.248+3205A>G		intron	N/A	NP_061116.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV6	ENST00000359396.9	TSL:1 MANE Select	c.248+3205A>G		intron	N/A	ENSP00000352358.5
	TRPV6	ENST00000436401.1	TSL:4	c.-68+3463A>G		intron	N/A	ENSP00000411100.1
	TRPV6	ENST00000615386.4	TSL:2	n.3206A>G		non_coding_transcript_exon	Exon 1 of 12

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

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0294 AC: 2 AN: 68

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.100 AC: 14 AN: 140

Other (OTH) AF: 0.00 AC: 0 AN: 12

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

African (AFR) AF: 0.533 AC: 22106 AN: 41440

American (AMR) AF: 0.102 AC: 1559 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5180

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4830

European-Finnish (FIN) AF: 0.0729 AC: 773 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5219 AN: 67994

Other (OTH) AF: 0.177 AC: 374 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.40
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4987622; hg19: chr7-142579929;