rs113100797

chr19-49196501-TGCTGCGGGGGCC-Tchr19-49196501-TGCTGCGGGGGCC-TGCTGCGGGGGCCGCTGCGGGGGCC

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_017636.4(TRPM4):c.2283_2294del(p.Cys763_Arg766del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00711 in 1,556,054 control chromosomes in the GnomAD database, including 669 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. C758C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.037 ( 339 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 330 hom. )

Consequence

TRPM4
NM_017636.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.36

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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_017636.4.

BP6

Variant 19-49196501-TGCTGCGGGGGCC-T is Benign according to our data. Variant chr19-49196501-TGCTGCGGGGGCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 415729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49196501-TGCTGCGGGGGCC-T is described in Lovd as [Benign]. Variant chr19-49196501-TGCTGCGGGGGCC-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM4	NM_017636.4 linkuse as main transcript	c.2283_2294del	p.Cys763_Arg766del	inframe_deletion	17/25	ENST00000252826.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM4	ENST00000252826.10 linkuse as main transcript	c.2283_2294del	p.Cys763_Arg766del	inframe_deletion	17/25	1	NM_017636.4	P1	Q8TD43-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5611

AN:

152062

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.00859

AC:

1356

AN:

157942

Hom.:

AF XY:

0.00673

AC XY:

577

AN XY:

85712

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00841

Gnomad ASJ exome

AF:

0.000357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000382

Gnomad FIN exome

AF:

0.0000940

Gnomad NFE exome

AF:

0.000588

Gnomad OTH exome

AF:

0.00633

GnomAD4 exome

AF:

0.00384

AC:

5392

AN:

1403874

Hom.:

330

AF XY:

0.00325

AC XY:

2258

AN XY:

693886

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.00858

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.0000272

Gnomad4 SAS exome

AF:

0.000412

Gnomad4 FIN exome

AF:

0.0000238

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0372

AC:

5664

AN:

152180

Hom.:

339

Cov.:

AF XY:

0.0365

AC XY:

2716

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.00283

Hom.:

Bravo

AF:

0.0426

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 18, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 17, 2023	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 25, 2016

- -

Progressive familial heart block type IB

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2016

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Restrictive cardiomyopathy;C0878544:Cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego

Jan 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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