rs72984209

Variant names:

• chr11-101455057-G-A
• rs72984209
• NM_004621.6:c.2529C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101455057-G-A
• chr11-101455057-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004621.6(TRPC6):​c.2529C>T​(p.Phe843Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,610,434 control chromosomes in the GnomAD database, including 9,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2912 hom., cov: 32)
  • Exomes 𝑓: 0.078 (6368 hom.)
• Consequence: TRPC6 NM_004621.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.187
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-101455057-G-A is Benign according to our data. Variant chr11-101455057-G-A is described in ClinVar as Benign. ClinVar VariationId is 259460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.187 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	NM_004621.6	MANE Select	c.2529C>T	p.Phe843Phe	synonymous	Exon 11 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.2181C>T	p.Phe727Phe	synonymous	Exon 9 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.2529C>T	p.Phe843Phe	synonymous	Exon 11 of 13	ENSP00000340913.3
	TRPC6	ENST00000360497.4	TSL:1	c.2364C>T	p.Phe788Phe	synonymous	Exon 10 of 12	ENSP00000353687.4
	TRPC6	ENST00000348423.8	TSL:1	c.2181C>T	p.Phe727Phe	synonymous	Exon 9 of 11	ENSP00000343672.4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22460 AN: 151944 Hom.: 2903 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.0826 AC: 20712 AN: 250668 AF XY: 0.0797

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.0564

Gnomad ASJ exome AF: 0.0912

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0430

Gnomad NFE exome AF: 0.0723

Gnomad OTH exome AF: 0.0868

GnomAD4 exome AF: 0.0782 AC: 114024 AN: 1458372 Hom.: 6368 Cov.: 30 AF XY: 0.0778 AC XY: 56438 AN XY: 725578

African (AFR) AF: 0.365 AC: 12127 AN: 33264

American (AMR) AF: 0.0612 AC: 2733 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 2110 AN: 26054

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39526

South Asian (SAS) AF: 0.0792 AC: 6822 AN: 86166

European-Finnish (FIN) AF: 0.0438 AC: 2338 AN: 53358

Middle Eastern (MID) AF: 0.156 AC: 897 AN: 5744

European-Non Finnish (NFE) AF: 0.0736 AC: 81617 AN: 1109396

Other (OTH) AF: 0.0892 AC: 5374 AN: 60216

GnomAD4 genome AF: 0.148 AC: 22503 AN: 152062 Hom.: 2912 Cov.: 32 AF XY: 0.143 AC XY: 10648 AN XY: 74336

African (AFR) AF: 0.350 AC: 14511 AN: 41438

American (AMR) AF: 0.0902 AC: 1377 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 281 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0809 AC: 390 AN: 4822

European-Finnish (FIN) AF: 0.0438 AC: 464 AN: 10598

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5042 AN: 67960

Other (OTH) AF: 0.138 AC: 291 AN: 2110

Alfa AF: 0.0970 Hom.: 902

Bravo AF: 0.159

Asia WGS AF: 0.0580 AC: 202 AN: 3474

EpiCase AF: 0.0804

EpiControl AF: 0.0841

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Focal segmental glomerulosclerosis 2 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.0
DANN	Benign	0.45
PhyloP100		0.19
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: rs72984209; hg19: chr11-101325788; COSMIC: COSV60255420;