dbSNP rs7621642: TRPC1:p.Ser340Ser (chr3-142784763-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001251845.2(TRPC1):c.1020G>A(p.Ser340Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,613,628 control chromosomes in the GnomAD database, including 55,615 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 0.35 ( 12693 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42922 hom. )

Consequence

TRPC1
NM_001251845.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

Publications

23 publications found

Variant links:

Genes affected

TRPC1 (HGNC:12333): (transient receptor potential cation channel subfamily C member 1) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

TRPC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.019 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2 link	c.1020G>A	p.Ser340Ser	synonymous_variant	Exon 7 of 13	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TRPC1	ENST00000476941.6 link	c.1020G>A	p.Ser340Ser	synonymous_variant	Exon 7 of 13	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10 link	c.918G>A	p.Ser306Ser	synonymous_variant	Exon 6 of 12	1		ENSP00000273482.6
TRPC1	ENST00000698238.1 link	c.1329G>A	p.Ser443Ser	synonymous_variant	Exon 7 of 13			ENSP00000513620.1
TRPC1	ENST00000480101.1 link	n.150G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52818

AN:

151906

Hom.:

12642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.246

AC:

61861

AN:

251134

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.227

AC:

331665

AN:

1461604

Hom.:

42922

Cov.:

AF XY:

0.223

AC XY:

162488

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.711

AC:

23808

AN:

33470

American (AMR)

AF:

0.190

AC:

8514

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3170

AN:

26128

East Asian (EAS)

AF:

0.376

AC:

14923

AN:

39678

South Asian (SAS)

AF:

0.207

AC:

17892

AN:

86246

European-Finnish (FIN)

AF:

0.202

AC:

10794

AN:

53402

Middle Eastern (MID)

AF:

0.171

AC:

989

AN:

5768

European-Non Finnish (NFE)

AF:

0.213

AC:

236572

AN:

1111814

Other (OTH)

AF:

0.248

AC:

15003

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

13409

26819

40228

53638

67047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8482

16964

25446

33928

42410

<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:

0.348

AC:

52927

AN:

152024

Hom.:

12693

Cov.:

AF XY:

0.343

AC XY:

25489

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.690

AC:

28572

AN:

41424

American (AMR)

AF:

0.215

AC:

3277

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

433

AN:

3472

East Asian (EAS)

AF:

0.432

AC:

2235

AN:

5174

South Asian (SAS)

AF:

0.211

AC:

1018

AN:

4820

European-Finnish (FIN)

AF:

0.202

AC:

2138

AN:

10570

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14390

AN:

67976

Other (OTH)

AF:

0.303

AC:

639

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1305

2610

3915

5220

6525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.252

Hom.:

21530

Bravo

AF:

0.365

Asia WGS

AF:

0.348

AC:

1211

AN:

3478

EpiCase

AF:

0.209

EpiControl

AF:

0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.4

(source)

DANN

Benign

0.71

PhyloP100

-0.019

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over