rs113100797

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_017636.4(TRPM4):c.2283_2294delCCGCTGCGGGGG(p.Arg762_Gly765del) variant causes a disruptive 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 339 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 330 hom. )

Consequence

TRPM4
NM_017636.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 4.36

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

erythrokeratodermia variabilis et progressiva 6
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
progressive familial heart block type IB
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
erythrokeratodermia variabilis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
progressive familial heart block
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

TRPM4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 415729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
TRPM4	NM_017636.4 link	c.2283_2294delCCGCTGCGGGGG	p.Arg762_Gly765del	disruptive_inframe_deletion	Exon 17 of 25	ENST00000252826.10	NP_060106.2	Q8TD43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM4	ENST00000252826.10 link	c.2283_2294delCCGCTGCGGGGG	p.Arg762_Gly765del	disruptive_inframe_deletion	Exon 17 of 25	1	NM_017636.4	ENSP00000252826.4		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

GnomAD2 exomes

AF:

0.00859

AC:

1356

AN:

157942

AF XY:

0.00673

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 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

African (AFR)

AF:

0.130

AC:

4175

AN:

32226

American (AMR)

AF:

0.00858

AC:

318

AN:

37084

Ashkenazi Jewish (ASJ)

AF:

0.0000795

AC:

AN:

25170

East Asian (EAS)

AF:

0.0000272

AC:

AN:

36802

South Asian (SAS)

AF:

0.000412

AC:

AN:

80108

European-Finnish (FIN)

AF:

0.0000238

AC:

AN:

41978

Middle Eastern (MID)

AF:

0.00596

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.000214

AC:

232

AN:

1086398

Other (OTH)

AF:

0.0102

AC:

596

AN:

58404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

238

477

715

954

1192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0372

AC:

5664

AN:

152180

Hom.:

339

Cov.:

AF XY:

0.0365

AC XY:

2716

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.127

AC:

5253

AN:

41514

American (AMR)

AF:

0.0196

AC:

300

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.000623

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

67992

Other (OTH)

AF:

0.0317

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

228

456

685

913

1141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

May 18, 2017

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 17, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 25, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive familial heart block type IB

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 07, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 22, 2019

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.4

Mutation Taster

=132/68

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over