rs145077205

Variant names:

• chr11-101472200-C-A
• rs145077205
• NM_004621.6:c.2142G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101472200-C-A
• chr11-101472200-C-T
• chr11-101472200-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_004621.6(TRPC6):​c.2142G>T​(p.Thr714Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,612,764 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T714T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (51 hom.)
• Consequence: TRPC6 NM_004621.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: 0.119
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 11-101472200-C-A is Benign according to our data. Variant chr11-101472200-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 236162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.119 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00405 (616/152208) while in subpopulation SAS AF = 0.017 (82/4824). AF 95% confidence interval is 0.014. There are 3 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 616 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.2142G>T	p.Thr714Thr	synonymous	Exon 8 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.1794G>T	p.Thr598Thr	synonymous	Exon 6 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.2142G>T	p.Thr714Thr	synonymous	Exon 8 of 13	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000360497.4	TSL:1	c.1977G>T	p.Thr659Thr	synonymous	Exon 7 of 12	ENSP00000353687.4	Q9Y210-3
	TRPC6	ENST00000348423.8	TSL:1	c.1794G>T	p.Thr598Thr	synonymous	Exon 6 of 11	ENSP00000343672.4	Q9Y210-2

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 619 AN: 152090 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.000945

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00501

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00581 AC: 1455 AN: 250504 AF XY: 0.00715

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00646

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000883

Gnomad NFE exome AF: 0.00555

Gnomad OTH exome AF: 0.00557

GnomAD4 exome AF: 0.00536 AC: 7828 AN: 1460556 Hom.: 51 Cov.: 31 AF XY: 0.00594 AC XY: 4313 AN XY: 726616

African (AFR) AF: 0.000688 AC: 23 AN: 33434

American (AMR) AF: 0.00342 AC: 153 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00678 AC: 177 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0199 AC: 1712 AN: 86214

European-Finnish (FIN) AF: 0.00124 AC: 66 AN: 53308

Middle Eastern (MID) AF: 0.0201 AC: 108 AN: 5384

European-Non Finnish (NFE) AF: 0.00468 AC: 5206 AN: 1111438

Other (OTH) AF: 0.00635 AC: 383 AN: 60318

GnomAD4 genome AF: 0.00405 AC: 616 AN: 152208 Hom.: 3 Cov.: 32 AF XY: 0.00415 AC XY: 309 AN XY: 74402

African (AFR) AF: 0.000746 AC: 31 AN: 41546

American (AMR) AF: 0.00648 AC: 99 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4824

European-Finnish (FIN) AF: 0.000945 AC: 10 AN: 10580

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00501 AC: 341 AN: 67998

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00307 Hom.: 1

Bravo AF: 0.00369

EpiCase AF: 0.00764

EpiControl AF: 0.00747

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Focal segmental glomerulosclerosis (1)
-	-	1	Focal segmental glomerulosclerosis 2 (1)
-	-	1	not specified (1)
-	-	-	Prednisolone response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	0.15
DANN	Benign	0.61
PhyloP100		0.12
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: rs145077205; hg19: chr11-101342931; COSMIC: COSV60257570;