rs56134796

Variant names:

• chr11-101583721-G-A
• rs56134796
• NM_004621.6:c.-218C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101583721-G-A
• chr11-101583721-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004621.6(TRPC6):​c.-218C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 472,656 control chromosomes in the GnomAD database, including 12,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3537 hom., cov: 33)
  • Exomes 𝑓: 0.22 (8646 hom.)
• Consequence: TRPC6 NM_004621.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.325
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-101583721-G-A is Benign according to our data. Variant chr11-101583721-G-A is described in ClinVar as Benign. ClinVar VariationId is 301918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 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.-218C>T		5_prime_UTR	Exon 1 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.-218C>T		5_prime_UTR	Exon 1 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.-218C>T		5_prime_UTR	Exon 1 of 13	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000893221.1		c.-218C>T		5_prime_UTR	Exon 1 of 13	ENSP00000563280.1
	TRPC6	ENST00000893220.1		c.-218C>T		5_prime_UTR	Exon 1 of 12	ENSP00000563279.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30391 AN: 152076 Hom.: 3538 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.216 AC: 69338 AN: 320462 Hom.: 8646 Cov.: 4 AF XY: 0.216 AC XY: 35448 AN XY: 164182

African (AFR) AF: 0.122 AC: 926 AN: 7614

American (AMR) AF: 0.157 AC: 1346 AN: 8600

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 2779 AN: 10380

East Asian (EAS) AF: 0.000128 AC: 3 AN: 23514

South Asian (SAS) AF: 0.112 AC: 1668 AN: 14868

European-Finnish (FIN) AF: 0.254 AC: 6269 AN: 24654

Middle Eastern (MID) AF: 0.306 AC: 461 AN: 1508

European-Non Finnish (NFE) AF: 0.247 AC: 51740 AN: 209744

Other (OTH) AF: 0.212 AC: 4146 AN: 19580

GnomAD4 genome AF: 0.200 AC: 30380 AN: 152194 Hom.: 3537 Cov.: 33 AF XY: 0.199 AC XY: 14795 AN XY: 74426

African (AFR) AF: 0.118 AC: 4916 AN: 41542

American (AMR) AF: 0.171 AC: 2611 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5156

South Asian (SAS) AF: 0.123 AC: 596 AN: 4828

European-Finnish (FIN) AF: 0.275 AC: 2921 AN: 10606

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17395 AN: 67974

Other (OTH) AF: 0.217 AC: 458 AN: 2112

Alfa AF: 0.215 Hom.: 708

Bravo AF: 0.191

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.3
DANN	Benign	0.87
PhyloP100		0.33
PromoterAI		-0.034	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56134796; hg19: chr11-101454452;