Genetic Variant NM_001251845.2:c.2154+83G>A (chr3-142804713-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001251845.2(TRPC1):c.2154+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,331,468 control chromosomes in the GnomAD database, including 37,072 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 0.31 ( 10321 hom., cov: 32)

Exomes 𝑓: 0.20 ( 26751 hom. )

Consequence

TRPC1
NM_001251845.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.144

Publications

9 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251845.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRPC1	NM_001251845.2	MANE Select	c.2154+83G>A	intron	N/A	NP_001238774.1
TRPC1	NM_003304.5		c.2052+83G>A	intron	N/A	NP_003295.1
TRPC1	NM_001413361.1		c.2004+83G>A	intron	N/A	NP_001400290.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRPC1	ENST00000476941.6	TSL:1 MANE Select	c.2154+83G>A	intron	N/A	ENSP00000419313.1
TRPC1	ENST00000273482.10	TSL:1	c.2052+83G>A	intron	N/A	ENSP00000273482.6
TRPC1	ENST00000698238.1		c.2463+83G>A	intron	N/A	ENSP00000513620.1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47197

AN:

151936

Hom.:

10302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.200

AC:

236058

AN:

1179414

Hom.:

26751

AF XY:

0.196

AC XY:

115462

AN XY:

588312

show subpopulations

African (AFR)

AF:

0.651

AC:

16969

AN:

26052

American (AMR)

AF:

0.182

AC:

5140

AN:

28290

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2133

AN:

19216

East Asian (EAS)

AF:

0.234

AC:

8502

AN:

36282

South Asian (SAS)

AF:

0.155

AC:

9780

AN:

63256

European-Finnish (FIN)

AF:

0.179

AC:

8650

AN:

48406

Middle Eastern (MID)

AF:

0.154

AC:

672

AN:

4360

European-Non Finnish (NFE)

AF:

0.192

AC:

173319

AN:

903398

Other (OTH)

AF:

0.217

AC:

10893

AN:

50154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

8680

17360

26040

34720

43400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6084

12168

18252

24336

30420

<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:

0.311

AC:

47257

AN:

152054

Hom.:

10321

Cov.:

AF XY:

0.305

AC XY:

22644

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.631

AC:

26178

AN:

41468

American (AMR)

AF:

0.198

AC:

3021

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

402

AN:

3466

East Asian (EAS)

AF:

0.277

AC:

1435

AN:

5178

South Asian (SAS)

AF:

0.154

AC:

740

AN:

4818

European-Finnish (FIN)

AF:

0.179

AC:

1892

AN:

10562

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.189

AC:

12814

AN:

67976

Other (OTH)

AF:

0.267

AC:

562

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1383

2766

4149

5532

6915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.215

Hom.:

2430

Bravo

AF:

0.327

Asia WGS

AF:

0.251

AC:

876

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.82

PhyloP100

0.14

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over