NM_004621.6:c.171-7438G>A

Variant names:

• chr11-101512236-C-T
• rs7925012
• NM_004621.6:c.171-7438G>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.171-7438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,940 control chromosomes in the GnomAD database, including 18,629 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 0.49 (18629 hom., cov: 32)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 4 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 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.171-7438G>A		intron	N/A	NP_004612.2
	TRPC6	NM_001439335.1		c.171-7438G>A		intron	N/A	NP_001426264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.171-7438G>A		intron	N/A	ENSP00000340913.3
	TRPC6	ENST00000360497.4	TSL:1	c.171-7438G>A		intron	N/A	ENSP00000353687.4
	TRPC6	ENST00000348423.8	TSL:1	c.171-7438G>A		intron	N/A	ENSP00000343672.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74344 AN: 151824 Hom.: 18615 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.490 AC: 74417 AN: 151940 Hom.: 18629 Cov.: 32 AF XY: 0.489 AC XY: 36306 AN XY: 74234

African (AFR) AF: 0.549 AC: 22735 AN: 41400

American (AMR) AF: 0.414 AC: 6327 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1085 AN: 5162

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4814

European-Finnish (FIN) AF: 0.538 AC: 5683 AN: 10568

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33305 AN: 67942

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.492 Hom.: 9757

Bravo AF: 0.483

Asia WGS AF: 0.335 AC: 1166 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.8
DANN	Benign	0.81
PhyloP100		-0.61
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: rs7925012; hg19: chr11-101382967;