rs4531428

Variant names:

• chr11-101541308-A-G
• rs4531428
• NM_004621.6:c.171-36510T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-101541308-A-G
• chr11-101541308-A-T

Variant summary

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

The NM_004621.6(TRPC6):​c.171-36510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,112 control chromosomes in the GnomAD database, including 41,722 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 0.74 (41722 hom., cov: 33)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 1 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]

TRPC6 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.171-36510T>C		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	c.171-36510T>C		intron_variant	Intron 1 of 12	1	NM_004621.6	ENSP00000340913.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111845 AN: 151994 Hom.: 41684 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.747

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.736 AC: 111941 AN: 152112 Hom.: 41722 Cov.: 33 AF XY: 0.736 AC XY: 54737 AN XY: 74346

African (AFR) AF: 0.633 AC: 26260 AN: 41490

American (AMR) AF: 0.693 AC: 10599 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2724 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3071 AN: 5160

South Asian (SAS) AF: 0.829 AC: 3999 AN: 4822

European-Finnish (FIN) AF: 0.769 AC: 8125 AN: 10566

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54527 AN: 67992

Other (OTH) AF: 0.750 AC: 1583 AN: 2110

Alfa AF: 0.790 Hom.: 24138

Bravo AF: 0.726

Asia WGS AF: 0.705 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.1
DANN	Benign	0.57
PhyloP100		-0.12
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: rs4531428; hg19: chr11-101412039;