chr11-69104326-C-T

Variant names:

• chr11-69104326-C-T
• rs930782
• ENST00000637084.1:n.*413+15960C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637084.1(ENSG00000287725):​n.*413+15960C>T variant causes a intron 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: ENSG00000287725 ENST00000637084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 6 publications found

Genes affected

ENSG00000287725 (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]

TPCN2 Gene-Disease associations (from GenCC):

• albinism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637084.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000287725	ENST00000637084.1	TSL:1	n.*413+15960C>T		intron	N/A	ENSP00000490615.1	A0A1B0GVQ7
	TPCN2	ENST00000637342.1	TSL:5	c.2003+18396C>T		intron	N/A	ENSP00000490171.1	A0A1B0GUM5
	TPCN2	ENST00000637504.1	TSL:5	c.*33+19040C>T		intron	N/A	ENSP00000489759.1	A0A1B0GTM1

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

African (AFR) AF: 0.117 AC: 4840 AN: 41534

American (AMR) AF: 0.152 AC: 2327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1298 AN: 5178

South Asian (SAS) AF: 0.122 AC: 588 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3187 AN: 10574

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15803 AN: 67976

Other (OTH) AF: 0.169 AC: 356 AN: 2112

Alfa AF: 0.219 Hom.: 1911

Bravo AF: 0.180

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-0.021

Splicing

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

Other links and lift over

dbSNP: rs930782; hg19: chr11-68871794;