11-2416195-T-G

Position:

• chr11-2416195-T-G

Variant summary

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

The NM_014555.4(TRPM5):​c.1010-171A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,092 control chromosomes in the GnomAD database, including 18,764 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 0.49 (18764 hom., cov: 34)
• Consequence: TRPM5 NM_014555.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM5	NM_014555.4	c.1010-171A>C		intron_variant		ENST00000696290.1	NP_055370.1
TRPM5	XM_047426859.1	c.-311A>C		5_prime_UTR_variant	1/17		XP_047282815.1
TRPM5	XM_017017628.2	c.1064-171A>C		intron_variant			XP_016873117.1
TRPM5	XM_047426858.1	c.1064-171A>C		intron_variant			XP_047282814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM5	ENST00000696290.1	c.1010-171A>C		intron_variant			NM_014555.4	ENSP00000512529.1
TRPM5	ENST00000533060.5	c.1010-171A>C		intron_variant		1		ENSP00000434121.1
TRPM5	ENST00000528453.1	c.1010-171A>C		intron_variant		1		ENSP00000436809.1
TRPM5	ENST00000533881.5	c.992-171A>C		intron_variant		1		ENSP00000434383.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75075 AN: 151974 Hom.: 18739 Cov.: 34

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.494 AC: 75136 AN: 152092 Hom.: 18764 Cov.: 34 AF XY: 0.490 AC XY: 36459 AN XY: 74334

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.483

Alfa AF: 0.489 Hom.: 26447

Bravo AF: 0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.62

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: rs2301698; hg19: chr11-2437425;