rs11224779

Variant names:

• chr11-101472631-C-T
• rs11224779
• NM_004621.6:c.2010-299G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004621.6(TRPC6):​c.2010-299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,016 control chromosomes in the GnomAD database, including 9,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (9525 hom., cov: 32)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.87
• 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]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-101472631-C-T is Benign according to our data. Variant chr11-101472631-C-T is described in ClinVar as [Benign]. Clinvar id is 1253314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.2010-299G>A		intron_variant	Intron 7 of 12	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.2010-299G>A		intron_variant	Intron 7 of 12	1	NM_004621.6	ENSP00000340913.3
TRPC6	ENST00000360497.4	c.1845-299G>A		intron_variant	Intron 6 of 11	1		ENSP00000353687.4
TRPC6	ENST00000348423.8	c.1662-299G>A		intron_variant	Intron 5 of 10	1		ENSP00000343672.4
TRPC6	ENST00000532133.5	c.1776-299G>A		intron_variant	Intron 6 of 11	5		ENSP00000435574.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48360 AN: 151898 Hom.: 9497 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.319 AC: 48446 AN: 152016 Hom.: 9525 Cov.: 32 AF XY: 0.312 AC XY: 23192 AN XY: 74326

African (AFR) AF: 0.561 AC: 23247 AN: 41462

American (AMR) AF: 0.207 AC: 3157 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3464

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5176

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2079 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16745 AN: 67942

Other (OTH) AF: 0.304 AC: 642 AN: 2110

Alfa AF: 0.285 Hom.: 934

Bravo AF: 0.327

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.73
PhyloP100		-1.9
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: rs11224779; hg19: chr11-101343362;