Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000252826.10(TRPM4):c.306T>G(p.Val102Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,566,752 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 37 hom. )

Consequence

TRPM4
ENST00000252826.10 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.436

Publications

0 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 19-49167955-T-G is Benign according to our data. Variant chr19-49167955-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 220960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.436 with no splicing effect.

BS2

High AC in GnomAd4 at 987 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252826.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRPM4	NM_017636.4	MANE Select	c.306T>G	p.Val102Val	synonymous	Exon 4 of 25	NP_060106.2
TRPM4	NM_001195227.2		c.306T>G	p.Val102Val	synonymous	Exon 4 of 24	NP_001182156.1
TRPM4	NM_001321281.2		c.268-598T>G		intron	N/A	NP_001308210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRPM4	ENST00000252826.10	TSL:1 MANE Select	c.306T>G	p.Val102Val	synonymous	Exon 4 of 25	ENSP00000252826.4
TRPM4	ENST00000427978.6	TSL:1	c.306T>G	p.Val102Val	synonymous	Exon 4 of 24	ENSP00000407492.1
TRPM4	ENST00000595519.5	TSL:1	n.93-305T>G		intron	N/A	ENSP00000469893.1

Frequencies

GnomAD3 genomes

AF:

0.00663

AC:

986

AN:

148680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00257

Gnomad ASJ

AF:

0.0123

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0109

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00980

Gnomad NFE

AF:

0.00755

Gnomad OTH

AF:

0.00340

GnomAD2 exomes

AF:

0.0000786

AC:

AN:

241648

AF XY:

0.0000767

show subpopulations

Gnomad AFR exome

AF:

0.000442

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000347

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.00163

AC:

2314

AN:

1417958

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1315

AN XY:

704414

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

32770

American (AMR)

AF:

0.000972

AC:

AN:

44216

Ashkenazi Jewish (ASJ)

AF:

0.00507

AC:

126

AN:

24872

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00432

AC:

351

AN:

81194

European-Finnish (FIN)

AF:

0.00530

AC:

267

AN:

50378

Middle Eastern (MID)

AF:

0.00267

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.00124

AC:

1337

AN:

1080550

Other (OTH)

AF:

0.00174

AC:

102

AN:

58668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

157

314

472

629

786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00663

AC:

987

AN:

148794

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

497

AN XY:

72638

show subpopulations

African (AFR)

AF:

0.00565

AC:

231

AN:

40908

American (AMR)

AF:

0.00257

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

AN:

3324

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.0109

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.0115

AC:

116

AN:

10104

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00755

AC:

500

AN:

66258

Other (OTH)

AF:

0.00337

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0154

Hom.:

Bravo

AF:

0.0145

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Progressive familial heart block type IB (2)

Cardiovascular phenotype (1)

TRPM4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.4

(source)

DANN

Benign

0.70

PhyloP100

-0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs111783027

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over