12-109807783-A-G

Position:

• chr12-109807783-A-G

Variant summary

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

The NM_021625.5(TRPV4):​c.559+513T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,930 control chromosomes in the GnomAD database, including 31,420 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 0.63 (31420 hom., cov: 31)
• Consequence: TRPV4 NM_021625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV4	NM_021625.5	c.559+513T>C		intron_variant		ENST00000261740.7	NP_067638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV4	ENST00000261740.7	c.559+513T>C		intron_variant		1	NM_021625.5	ENSP00000261740.2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95352 AN: 151812 Hom.: 31355 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.628 AC: 95476 AN: 151930 Hom.: 31420 Cov.: 31 AF XY: 0.636 AC XY: 47197 AN XY: 74260

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.603

Alfa AF: 0.536 Hom.: 33657

Bravo AF: 0.642

Asia WGS AF: 0.836 AC: 2905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.64
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1861809; hg19: chr12-110245588;