rs930782

Positions:

• chr11-69104326-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000567925.1(ENSG00000260895):​n.380+454C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,162 control chromosomes in the GnomAD database, including 3,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3121 hom., cov: 33)
• Consequence: ENST00000567925.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

Genes affected

(HGNC:):

TPCN2 (HGNC:20820): (two pore segment channel 2) This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000567925.1	n.380+454C>T		intron_variant, non_coding_transcript_variant		3
TPCN2	ENST00000637342.1	c.2003+18396C>T		intron_variant		5
TPCN2	ENST00000637504.1	c.*33+19040C>T		intron_variant		5
TPCN2	ENST00000635811.1	c.*867+15960C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29386 AN: 152044 Hom.: 3121 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29382 AN: 152162 Hom.: 3121 Cov.: 33 AF XY: 0.194 AC XY: 14433 AN XY: 74390

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.169

Alfa AF: 0.212 Hom.: 1107

Bravo AF: 0.180

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs930782; hg19: chr11-68871794;