NM_004621.6:c.2485-138C>T

Variant names:

• chr11-101455239-G-A
• rs7105083
• NM_004621.6:c.2485-138C>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.2485-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 696,594 control chromosomes in the GnomAD database, including 24,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (9617 hom., cov: 32)
  • Exomes 𝑓: 0.22 (15307 hom.)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.50
• Publications: 2 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=-0.99).
• BP6: Variant 11-101455239-G-A is Benign according to our data. Variant chr11-101455239-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.2485-138C>T		intron_variant	Intron 10 of 12	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.2485-138C>T		intron_variant	Intron 10 of 12	1	NM_004621.6	ENSP00000340913.3

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47310 AN: 151936 Hom.: 9584 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.224 AC: 121871 AN: 544540 Hom.: 15307 Cov.: 7 AF XY: 0.224 AC XY: 65111 AN XY: 290696

African (AFR) AF: 0.584 AC: 8023 AN: 13744

American (AMR) AF: 0.149 AC: 3843 AN: 25716

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 4200 AN: 16082

East Asian (EAS) AF: 0.128 AC: 3879 AN: 30232

South Asian (SAS) AF: 0.241 AC: 12614 AN: 52334

European-Finnish (FIN) AF: 0.159 AC: 5451 AN: 34356

Middle Eastern (MID) AF: 0.344 AC: 838 AN: 2438

European-Non Finnish (NFE) AF: 0.223 AC: 76013 AN: 340934

Other (OTH) AF: 0.244 AC: 7010 AN: 28704

GnomAD4 genome AF: 0.312 AC: 47399 AN: 152054 Hom.: 9617 Cov.: 32 AF XY: 0.304 AC XY: 22583 AN XY: 74326

African (AFR) AF: 0.581 AC: 24082 AN: 41440

American (AMR) AF: 0.197 AC: 3007 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3470

East Asian (EAS) AF: 0.0658 AC: 341 AN: 5180

South Asian (SAS) AF: 0.227 AC: 1098 AN: 4832

European-Finnish (FIN) AF: 0.150 AC: 1587 AN: 10566

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15449 AN: 67988

Other (OTH) AF: 0.308 AC: 650 AN: 2110

Alfa AF: 0.287 Hom.: 1059

Bravo AF: 0.324

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.010
DANN	Benign	0.18
PhyloP100		-2.5
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: rs7105083; hg19: chr11-101325970;