12-109796853-T-C

Position:

• chr12-109796853-T-C

Variant summary

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

The NM_021625.5(TRPV4):​c.1153-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 811,798 control chromosomes in the GnomAD database, including 39,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6202 hom., cov: 32)
  • Exomes 𝑓: 0.30 (33216 hom.)
• Consequence: TRPV4 NM_021625.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

Genes affected

TRPV4 (HGNC:18083): (transient receptor potential cation channel subfamily V member 4) This gene encodes a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels. The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure. Mutations in this gene are the cause of spondylometaphyseal and metatropic dysplasia and hereditary motor and sensory neuropathy type IIC. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-109796853-T-C is Benign according to our data. Variant chr12-109796853-T-C is described in ClinVar as [Benign]. Clinvar id is 670253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV4	NM_021625.5	c.1153-149A>G		intron_variant		ENST00000261740.7	NP_067638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV4	ENST00000261740.7	c.1153-149A>G		intron_variant		1	NM_021625.5	ENSP00000261740	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39773 AN: 151976 Hom.: 6196 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.297 AC: 196217 AN: 659704 Hom.: 33216 AF XY: 0.297 AC XY: 98780 AN XY: 332414

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.687

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.262 AC: 39783 AN: 152094 Hom.: 6202 Cov.: 32 AF XY: 0.269 AC XY: 20011 AN XY: 74330

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.265

Alfa AF: 0.289 Hom.: 11148

Bravo AF: 0.252

Asia WGS AF: 0.376 AC: 1307 AN: 3478

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

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.39

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: rs3742035; hg19: chr12-110234658;