Variant chr19-49157760-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The ENST00000598691.5(TRPM4):c.-107G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,470,546 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 29 hom. )

Consequence

TRPM4
ENST00000598691.5 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.724

Variant links:

Genes affected

TRPM4 (HGNC:17993): (transient receptor potential cation channel subfamily M member 4) The protein encoded by this gene is a calcium-activated nonselective ion channel that mediates transport of monovalent cations across membranes, thereby depolarizing the membrane. The activity of the encoded protein increases with increasing intracellular calcium concentration, but this channel does not transport calcium. [provided by RefSeq, Mar 2016]

TRPM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 19-49157760-G-T is Benign according to our data. Variant chr19-49157760-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 329838.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00286 (435/152312) while in subpopulation SAS AF= 0.0124 (60/4828). AF 95% confidence interval is 0.00991. There are 5 homozygotes in gnomad4. There are 240 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 435 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM4	NM_017636.4 linkuse as main transcript			upstream_gene_variant		ENST00000252826.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM4	ENST00000252826.10 linkuse as main transcript			upstream_gene_variant		1	NM_017636.4	P1	Q8TD43-1

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.00186

AC:

2446

AN:

1318234

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

1545

AN XY:

651060

show subpopulations

Gnomad4 AFR exome

AF:

0.00736

Gnomad4 AMR exome

AF:

0.000662

Gnomad4 ASJ exome

AF:

0.000371

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.000120

Gnomad4 NFE exome

AF:

0.000667

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152312

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00691

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00280

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	TRPM4: BS1, BS2 -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Progressive familial heart block

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over