12-109790160-C-T

Position:

• chr12-109790160-C-T

Variant summary

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

The NM_021625.5(TRPV4):​c.1892-1444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,000 control chromosomes in the GnomAD database, including 17,782 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 0.48 (17782 hom., cov: 32)
• Consequence: TRPV4 NM_021625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

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]

TRPV4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV4	NM_021625.5	c.1892-1444G>A		intron_variant		ENST00000261740.7	NP_067638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV4	ENST00000261740.7	c.1892-1444G>A		intron_variant		1	NM_021625.5	ENSP00000261740.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72378 AN: 151882 Hom.: 17762 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72434 AN: 152000 Hom.: 17782 Cov.: 32 AF XY: 0.485 AC XY: 36009 AN XY: 74278

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.500

Alfa AF: 0.497 Hom.: 25071

Bravo AF: 0.470

Asia WGS AF: 0.633 AC: 2197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
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: rs10735104; hg19: chr12-110227965;