11-101519716-A-T

Variant names:

• chr11-101519716-A-T
• rs12275715
• NM_004621.6:c.171-14918T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 2 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004621.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	NM_004621.6	MANE Select	c.171-14918T>A		intron	N/A	NP_004612.2
	TRPC6	NM_001439335.1		c.171-14918T>A		intron	N/A	NP_001426264.1
	MIR3920	NR_037485.1		n.*104T>A		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.171-14918T>A		intron	N/A	ENSP00000340913.3
	TRPC6	ENST00000360497.4	TSL:1	c.171-14918T>A		intron	N/A	ENSP00000353687.4
	TRPC6	ENST00000348423.8	TSL:1	c.171-14918T>A		intron	N/A	ENSP00000343672.4

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7370 AN: 151908 Hom.: 311 Cov.: 30

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: 91 AN: 1970 Hom.: 2 AF XY: 0.0388 AC XY: 39 AN XY: 1006

African (AFR) AF: 0.0806 AC: 5 AN: 62

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0294 AC: 2 AN: 68

European-Finnish (FIN) AF: 0.0579 AC: 14 AN: 242

Middle Eastern (MID) AF: 0.0483 AC: 61 AN: 1264

European-Non Finnish (NFE) AF: 0.0217 AC: 4 AN: 184

Other (OTH) AF: 0.0362 AC: 5 AN: 138

GnomAD4 genome AF: 0.0486 AC: 7387 AN: 152026 Hom.: 314 Cov.: 30 AF XY: 0.0489 AC XY: 3632 AN XY: 74312

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: 50 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 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: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1981 AN: 67972

Other (OTH) AF: 0.0341 AC: 72 AN: 2112

Alfa AF: 0.0420 Hom.: 23

Bravo AF: 0.0483

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12275715; hg19: chr11-101390447;