dbSNP rs12275715: TRPC6:c.171-14918T>A (chr11-101519716-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004621.6(TRPC6):c.171-14918T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 153,996 control chromosomes in the GnomAD database, including 316 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 0.049 ( 314 hom., cov: 30)

Exomes 𝑓: 0.046 ( 2 hom. )

Consequence

TRPC6
NM_004621.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

2 publications found

Variant links:

Genes affected

TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

TRPC6 links:

MIR3920 (HGNC:38974): (microRNA 3920) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3920 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.171-14918T>A		intron_variant	Intron 1 of 12	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 link	c.171-14918T>A		intron_variant	Intron 1 of 12	1	NM_004621.6	ENSP00000340913.3

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7370

AN:

151908

Hom.:

311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0344

GnomAD4 exome

AF:

0.0462

AC:

AN:

1970

Hom.:

AF XY:

0.0388

AC XY:

AN XY:

1006

show subpopulations

African (AFR)

AF:

0.0806

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0294

AC:

AN:

European-Finnish (FIN)

AF:

0.0579

AC:

AN:

242

Middle Eastern (MID)

AF:

0.0483

AC:

AN:

1264

European-Non Finnish (NFE)

AF:

0.0217

AC:

AN:

184

Other (OTH)

AF:

0.0362

AC:

AN:

138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

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:

0.0486

AC:

7387

AN:

152026

Hom.:

314

Cov.:

AF XY:

0.0489

AC XY:

3632

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.101

AC:

4196

AN:

41468

American (AMR)

AF:

0.0268

AC:

410

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.0223

AC:

107

AN:

4808

European-Finnish (FIN)

AF:

0.0527

AC:

558

AN:

10596

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0291

AC:

1981

AN:

67972

Other (OTH)

AF:

0.0341

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

321

641

962

1282

1603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0420

Hom.:

Bravo

AF:

0.0483

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.8

(source)

DANN

Benign

0.78

PhyloP100

1.8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over