11-2409635-C-T

Variant names:

• chr11-2409635-C-T
• rs800348
• NM_014555.4:c.2782+1717G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014555.4(TRPM5):​c.2782+1717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,094 control chromosomes in the GnomAD database, including 31,123 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 (31123 hom., cov: 33)
• Consequence: TRPM5 NM_014555.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014555.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	NM_014555.4	MANE Select	c.2782+1717G>A		intron	N/A	NP_055370.1	Q9NZQ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	ENST00000696290.1	MANE Select	c.2782+1717G>A		intron	N/A	ENSP00000512529.1	Q9NZQ8-1
	TRPM5	ENST00000533060.5	TSL:1	c.2782+1717G>A		intron	N/A	ENSP00000434121.1	E9PRW0
	TRPM5	ENST00000528453.1	TSL:1	c.2782+1717G>A		intron	N/A	ENSP00000436809.1	E9PQF7

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96139 AN: 151976 Hom.: 31080 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.633 AC: 96233 AN: 152094 Hom.: 31123 Cov.: 33 AF XY: 0.636 AC XY: 47315 AN XY: 74350

African (AFR) AF: 0.766 AC: 31783 AN: 41508

American (AMR) AF: 0.681 AC: 10400 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3792 AN: 5164

South Asian (SAS) AF: 0.592 AC: 2853 AN: 4822

European-Finnish (FIN) AF: 0.567 AC: 6002 AN: 10582

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37684 AN: 67964

Other (OTH) AF: 0.604 AC: 1273 AN: 2108

Alfa AF: 0.582 Hom.: 42623

Bravo AF: 0.648

Asia WGS AF: 0.634 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs800348; hg19: chr11-2430865; COSMIC: COSV50200634; COSMIC: COSV50200634;