rs2301699

Variant names:

• chr11-2422864-C-G
• rs2301699
• NM_014555.4:c.117+56G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2422864-C-G
• chr11-2422864-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.96).
• 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 rank	MANE	Protein	UniProt
TRPM5	NM_014555.4	c.117+56G>C		intron_variant	Intron 6 of 28	ENST00000696290.1	NP_055370.1
TRPM5	XM_017017628.2	c.171+56G>C		intron_variant	Intron 3 of 25		XP_016873117.1
TRPM5	XM_047426858.1	c.171+56G>C		intron_variant	Intron 3 of 25		XP_047282814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM5	ENST00000696290.1	c.117+56G>C		intron_variant	Intron 6 of 28		NM_014555.4	ENSP00000512529.1
TRPM5	ENST00000533060.5	c.117+56G>C		intron_variant	Intron 1 of 23	1		ENSP00000434121.1
TRPM5	ENST00000528453.1	c.117+56G>C		intron_variant	Intron 1 of 23	1		ENSP00000436809.1
TRPM5	ENST00000533881.5	c.93+56G>C		intron_variant	Intron 1 of 23	1		ENSP00000434383.1

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

African (AFR) AF: 0.261 AC: 7957 AN: 30454

American (AMR) AF: 0.342 AC: 15195 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 10322 AN: 25162

East Asian (EAS) AF: 0.181 AC: 7038 AN: 38976

South Asian (SAS) AF: 0.308 AC: 25641 AN: 83220

European-Finnish (FIN) AF: 0.278 AC: 14375 AN: 51630

Middle Eastern (MID) AF: 0.409 AC: 2228 AN: 5450

European-Non Finnish (NFE) AF: 0.272 AC: 264544 AN: 972926

Other (OTH) AF: 0.292 AC: 16237 AN: 55514

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

African (AFR) AF: 0.260 AC: 10783 AN: 41410

American (AMR) AF: 0.352 AC: 5380 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3464

East Asian (EAS) AF: 0.223 AC: 1147 AN: 5150

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4812

European-Finnish (FIN) AF: 0.289 AC: 3062 AN: 10590

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18936 AN: 67844

Other (OTH) AF: 0.317 AC: 666 AN: 2104

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
PhyloP100		-1.5
PromoterAI		-0.026	Neutral
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: rs2301699; hg19: chr11-2444094; COSMIC: COSV50159191;