rs1551305

Positions:

• chr11-69087765-G-A
• chr11-69087765-G-C
• chr11-69087765-G-T

Variant summary

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

The NM_139075.4(TPCN2):​c.2181-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 780,160 control chromosomes in the GnomAD database, including 79,865 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 0.45 (15684 hom., cov: 32)
  • Exomes 𝑓: 0.44 (64181 hom.)
• Consequence: TPCN2 NM_139075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPCN2	NM_139075.4	c.2181-110G>A		intron_variant		ENST00000294309.8	NP_620714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPCN2	ENST00000294309.8	c.2181-110G>A		intron_variant		1	NM_139075.4	ENSP00000294309	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68101 AN: 151938 Hom.: 15684 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.443 AC: 278517 AN: 628104 Hom.: 64181 AF XY: 0.436 AC XY: 142020 AN XY: 325592

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.484

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.448 AC: 68113 AN: 152056 Hom.: 15684 Cov.: 32 AF XY: 0.440 AC XY: 32686 AN XY: 74336

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.459

Alfa AF: 0.313 Hom.: 781

Bravo AF: 0.446

Asia WGS AF: 0.288 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1551305; hg19: chr11-68855233;