ENST00000637084.1:n.*413+11080G>A

Variant names:

• chr11-69099446-G-A
• rs2305498
• ENST00000637084.1:n.*413+11080G>A

Variant summary

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

The ENST00000637084.1(ENSG00000287725):​n.*413+11080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,218 control chromosomes in the GnomAD database, including 3,421 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 0.21 (3421 hom., cov: 33)
• Consequence: ENSG00000287725 ENST00000637084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950
• Publications: 18 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 (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287725	ENST00000637084.1	n.*413+11080G>A		intron_variant	Intron 13 of 14	1		ENSP00000490615.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31277 AN: 152100 Hom.: 3421 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.206 AC: 31294 AN: 152218 Hom.: 3421 Cov.: 33 AF XY: 0.216 AC XY: 16059 AN XY: 74416

African (AFR) AF: 0.191 AC: 7932 AN: 41528

American (AMR) AF: 0.215 AC: 3286 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5168

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4828

European-Finnish (FIN) AF: 0.324 AC: 3431 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12510 AN: 68010

Other (OTH) AF: 0.197 AC: 416 AN: 2116

Alfa AF: 0.199 Hom.: 1732

Bravo AF: 0.193

Asia WGS AF: 0.298 AC: 1033 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	6.4
DANN	Benign	0.55
PhyloP100		0.95

Splicing

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

Other links and lift over

dbSNP: rs2305498; hg19: chr11-68866914;