rs2301699

Positions:

• chr11-2422864-C-G

Variant summary

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

The NM_014555.4(TRPM5):​c.117+56G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,459,672 control chromosomes in the GnomAD database, including 58,794 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 0.28 (6367 hom., cov: 32)
  • Exomes 𝑓: 0.28 (52427 hom.)
• Consequence: TRPM5 NM_014555.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

TRPM5 (HGNC:14323): (transient receptor potential cation channel subfamily M member 5) This gene encodes a member of the transient receptor potential (TRP) protein family, which is a diverse group of proteins with structural features typical of ion channels. This protein plays an important role in taste transduction, and has characteristics of a calcium-activated, non-selective cation channel that carries Na+, K+, and Cs+ ions equally well, but not Ca(2+) ions. It is activated by lower concentrations of intracellular Ca(2+), and inhibited by higher concentrations. It is also a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. This gene is located within the Beckwith-Wiedemann syndrome critical region-1 on chromosome 11p15.5, and has been shown to be imprinted, with exclusive expression from the paternal allele. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM5	NM_014555.4	c.117+56G>C		intron_variant		ENST00000696290.1
TRPM5	XM_017017628.2	c.171+56G>C		intron_variant
TRPM5	XM_047426858.1	c.171+56G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM5	ENST00000696290.1	c.117+56G>C		intron_variant			NM_014555.4	P2
TRPM5	ENST00000528453.1	c.117+56G>C		intron_variant		1		A2
TRPM5	ENST00000533060.5	c.117+56G>C		intron_variant		1		A2
TRPM5	ENST00000533881.5	c.93+56G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43076 AN: 151734 Hom.: 6371 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.278 AC: 363537 AN: 1307820 Hom.: 52427 AF XY: 0.279 AC XY: 184023 AN XY: 658604

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.284 AC: 43085 AN: 151852 Hom.: 6367 Cov.: 32 AF XY: 0.287 AC XY: 21326 AN XY: 74234

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.317

Alfa AF: 0.280 Hom.: 861

Bravo AF: 0.287

Asia WGS AF: 0.267 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
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: rs2301699; hg19: chr11-2444094; COSMIC: COSV50159191;