chr11-2405754-G-C

Position:

• chr11-2405754-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM5	NM_014555.4	c.3325-161C>G		intron_variant		ENST00000696290.1
TRPM5	XM_017017628.2	c.3403-161C>G		intron_variant
TRPM5	XM_047426858.1	c.3379-161C>G		intron_variant
TRPM5	XM_047426859.1	c.2200-161C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM5	ENST00000696290.1	c.3325-161C>G		intron_variant			NM_014555.4	P2
	ENST00000433035.1	n.319+921G>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.463

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2301696; hg19: chr11-2426984;