rs371262137

Positions:

• chr11-101488918-CCAGGCTTCACATA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004621.6(TRPC6):​c.1293+6_1293+18del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000907 in 1,613,890 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (5 hom.)
• Consequence: TRPC6 NM_004621.6 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.94

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-101488918-CCAGGCTTCACATA-C is Benign according to our data. Variant chr11-101488918-CCAGGCTTCACATA-C is described in ClinVar as [Benign]. Clinvar id is 586845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00491 (748/152264) while in subpopulation AFR AF= 0.0172 (713/41536). AF 95% confidence interval is 0.0161. There are 8 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.1293+6_1293+18del		splice_donor_region_variant, intron_variant		ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.1293+6_1293+18del		splice_donor_region_variant, intron_variant		1	NM_004621.6	ENSP00000340913	P1
TRPC6	ENST00000348423.8	c.946-5766_946-5754del		intron_variant		1		ENSP00000343672
TRPC6	ENST00000360497.4	c.1128+2625_1128+2637del		intron_variant		1		ENSP00000353687
TRPC6	ENST00000532133.5	c.1293+6_1293+18del		splice_donor_region_variant, intron_variant		5		ENSP00000435574

Frequencies

GnomAD3 genomes AF: 0.00491 AC: 747 AN: 152146 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00121 AC: 304 AN: 250914 Hom.: 2 AF XY: 0.000899 AC XY: 122 AN XY: 135674

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000490 AC: 716 AN: 1461626 Hom.: 5 AF XY: 0.000396 AC XY: 288 AN XY: 727130

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00491 AC: 748 AN: 152264 Hom.: 8 Cov.: 33 AF XY: 0.00465 AC XY: 346 AN XY: 74452

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00264 Hom.: 1

Bravo AF: 0.00570

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371262137; hg19: chr11-101359649;