11-2405754-G-C

Variant names:

• chr11-2405754-G-C
• rs2301696
• NM_014555.4:c.3325-161C>G

Variant summary

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

The NM_014555.4(TRPM5):​c.3325-161C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,016 control chromosomes in the GnomAD database, including 15,318 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 0.43 (15318 hom., cov: 33)
• Consequence: TRPM5 NM_014555.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 16 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]

ENSG00000230483 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM5	NM_014555.4	c.3325-161C>G		intron_variant	Intron 27 of 28	ENST00000696290.1	NP_055370.1
TRPM5	XM_017017628.2	c.3403-161C>G		intron_variant	Intron 24 of 25		XP_016873117.1
TRPM5	XM_047426858.1	c.3379-161C>G		intron_variant	Intron 24 of 25		XP_047282814.1
TRPM5	XM_047426859.1	c.2200-161C>G		intron_variant	Intron 15 of 16		XP_047282815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM5	ENST00000696290.1	c.3325-161C>G		intron_variant	Intron 27 of 28		NM_014555.4	ENSP00000512529.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64884 AN: 151898 Hom.: 15328 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.427 AC: 64874 AN: 152016 Hom.: 15318 Cov.: 33 AF XY: 0.416 AC XY: 30896 AN XY: 74298

African (AFR) AF: 0.262 AC: 10883 AN: 41492

American (AMR) AF: 0.403 AC: 6160 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1043 AN: 5124

South Asian (SAS) AF: 0.269 AC: 1298 AN: 4824

European-Finnish (FIN) AF: 0.419 AC: 4424 AN: 10568

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37570 AN: 67930

Other (OTH) AF: 0.463 AC: 979 AN: 2114

Alfa AF: 0.351 Hom.: 1010

Bravo AF: 0.422

Asia WGS AF: 0.216 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.60
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2301696; hg19: chr11-2426984;