chr11-101452618-C-T

Variant names:

• chr11-101452618-C-T
• rs144714163
• NM_004621.6:c.*337G>A

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.*337G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000857 in 256,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TRPC6 NM_004621.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90
• Publications: 0 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=-0.92).
• BP6: Variant 11-101452618-C-T is Benign according to our data. Variant chr11-101452618-C-T is described in ClinVar as Benign. ClinVar VariationId is 301890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000591 (9/152274) while in subpopulation EAS AF = 0.00116 (6/5174). AF 95% confidence interval is 0.000505. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 9 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.*337G>A		3_prime_UTR	Exon 13 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.*337G>A		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.*337G>A		3_prime_UTR	Exon 13 of 13	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000893221.1		c.*337G>A		3_prime_UTR	Exon 13 of 13	ENSP00000563280.1
	TRPC6	ENST00000893220.1		c.*337G>A		3_prime_UTR	Exon 12 of 12	ENSP00000563279.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 13 AN: 104456 Hom.: 0 Cov.: 0 AF XY: 0.000161 AC XY: 9 AN XY: 55842

African (AFR) AF: 0.00 AC: 0 AN: 3074

American (AMR) AF: 0.00 AC: 0 AN: 4852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2760

East Asian (EAS) AF: 0.00205 AC: 11 AN: 5368

South Asian (SAS) AF: 0.00 AC: 0 AN: 14272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 352

European-Non Finnish (NFE) AF: 0.0000156 AC: 1 AN: 64050

Other (OTH) AF: 0.000187 AC: 1 AN: 5360

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152274 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74452

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000570 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.00289 AC: 10 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	-0.92
CADD	Benign	0.13
DANN	Benign	0.49
PhyloP100		-1.9

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: rs144714163; hg19: chr11-101323349;