rs3824934

Variant names:

• chr11-101583757-G-C
• rs3824934
• NM_004621.6:c.-254C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-101583757-G-C
• chr11-101583757-G-A
• chr11-101583757-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.-254C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 394,526 control chromosomes in the GnomAD database, including 4,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (1292 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2987 hom.)
• Consequence: TRPC6 NM_004621.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.330
• Publications: 18 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=-0.78).
• BP6: Variant 11-101583757-G-C is Benign according to our data. Variant chr11-101583757-G-C is described in ClinVar as Benign. ClinVar VariationId is 301920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 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.-254C>G		5_prime_UTR	Exon 1 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.-254C>G		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.-254C>G		5_prime_UTR	Exon 1 of 13	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000893221.1		c.-254C>G		5_prime_UTR	Exon 1 of 13	ENSP00000563280.1
	TRPC6	ENST00000893220.1		c.-254C>G		5_prime_UTR	Exon 1 of 12	ENSP00000563279.1

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14841 AN: 152140 Hom.: 1284 Cov.: 33

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.119 AC: 28829 AN: 242268 Hom.: 2987 Cov.: 3 AF XY: 0.117 AC XY: 14465 AN XY: 123120

African (AFR) AF: 0.0381 AC: 257 AN: 6750

American (AMR) AF: 0.183 AC: 1280 AN: 6984

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 833 AN: 8880

East Asian (EAS) AF: 0.423 AC: 9113 AN: 21560

South Asian (SAS) AF: 0.235 AC: 1057 AN: 4498

European-Finnish (FIN) AF: 0.0985 AC: 1983 AN: 20140

Middle Eastern (MID) AF: 0.0730 AC: 91 AN: 1246

European-Non Finnish (NFE) AF: 0.0796 AC: 12458 AN: 156434

Other (OTH) AF: 0.111 AC: 1757 AN: 15776

GnomAD4 genome AF: 0.0976 AC: 14859 AN: 152258 Hom.: 1292 Cov.: 33 AF XY: 0.105 AC XY: 7794 AN XY: 74460

African (AFR) AF: 0.0378 AC: 1570 AN: 41572

American (AMR) AF: 0.162 AC: 2480 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2379 AN: 5136

South Asian (SAS) AF: 0.268 AC: 1294 AN: 4824

European-Finnish (FIN) AF: 0.103 AC: 1094 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0804 AC: 5465 AN: 68012

Other (OTH) AF: 0.107 AC: 226 AN: 2114

Alfa AF: 0.0906 Hom.: 90

Bravo AF: 0.0996

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Atypical hemolytic-uremic syndrome (1)
-	-	1	Focal segmental glomerulosclerosis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		-0.33
PromoterAI		0.023	Neutral
Mutation Taster		=300/0	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: rs3824934; hg19: chr11-101454488;