rs1123608

Positions:

• chr11-69135852-G-T

Variant summary

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

The ENST00000637084.1(ENSG00000287725):​n.*511+320G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 206,208 control chromosomes in the GnomAD database, including 472 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 0.049 (303 hom., cov: 33)
  • Exomes 𝑓: 0.053 (169 hom.)
• Consequence: ENSG00000287725 ENST00000637084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.69135852G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000287725	ENST00000637084.1	n.*511+320G>T		intron_variant		1		ENSP00000490615.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7495 AN: 152162 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0531 AC: 2864 AN: 53928 Hom.: 169 Cov.: 0 AF XY: 0.0506 AC XY: 1368 AN XY: 27032

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0334

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0507

Gnomad4 NFE exome AF: 0.0298

Gnomad4 OTH exome AF: 0.0476

GnomAD4 genome AF: 0.0492 AC: 7493 AN: 152280 Hom.: 303 Cov.: 33 AF XY: 0.0525 AC XY: 3907 AN XY: 74462

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0348 Hom.: 30

Bravo AF: 0.0527

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1123608; hg19: chr11-68903320;