rs112916171

Variant names:

• chr11-101452425-A-G
• rs112916171
• NM_004621.6:c.*530T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004621.6(TRPC6):​c.*530T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 157,426 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00078 (0 hom.)
• Consequence: TRPC6 NM_004621.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.758
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-101452425-A-G is Benign according to our data. Variant chr11-101452425-A-G is described in ClinVar as Benign. ClinVar VariationId is 301888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00826 (1258/152298) while in subpopulation AFR AF = 0.0268 (1114/41578). AF 95% confidence interval is 0.0255. There are 17 homozygotes in GnomAd4. There are 617 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1258 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	NM_004621.6	MANE Select	c.*530T>C		3_prime_UTR	Exon 13 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.*530T>C		3_prime_UTR	Exon 11 of 11	NP_001426264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.*530T>C		3_prime_UTR	Exon 13 of 13	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000893221.1		c.*530T>C		3_prime_UTR	Exon 13 of 13	ENSP00000563280.1
	TRPC6	ENST00000893220.1		c.*530T>C		3_prime_UTR	Exon 12 of 12	ENSP00000563279.1

Frequencies

GnomAD3 genomes AF: 0.00826 AC: 1257 AN: 152182 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00525

GnomAD4 exome AF: 0.000780 AC: 4 AN: 5128 Hom.: 0 Cov.: 0 AF XY: 0.000745 AC XY: 2 AN XY: 2686

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00242 AC: 3 AN: 1242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 28

East Asian (EAS) AF: 0.00 AC: 0 AN: 190

South Asian (SAS) AF: 0.00 AC: 0 AN: 540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2894

Other (OTH) AF: 0.00538 AC: 1 AN: 186

GnomAD4 genome AF: 0.00826 AC: 1258 AN: 152298 Hom.: 17 Cov.: 33 AF XY: 0.00828 AC XY: 617 AN XY: 74480

African (AFR) AF: 0.0268 AC: 1114 AN: 41578

American (AMR) AF: 0.00621 AC: 95 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68020

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00424 Hom.: 3

Bravo AF: 0.00958

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.093
DANN	Benign	0.38
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism

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: rs112916171; hg19: chr11-101323156;