rs10197851

Positions:

• chr2-10345283-A-G
• chr2-10345283-A-T

Variant summary

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

The NM_002149.4(HPCAL1):​c.-111+42106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,838 control chromosomes in the GnomAD database, including 21,733 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 0.51 (21733 hom., cov: 30)
• Consequence: HPCAL1 NM_002149.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

Genes affected

HPCAL1 (HGNC:5145): (hippocalcin like 1) The protein encoded by this gene is a member of neuron-specific calcium-binding proteins family found in the retina and brain. It is highly similar to human hippocalcin protein and nearly identical to the rat and mouse hippocalcin like-1 proteins. It may be involved in the calcium-dependent regulation of rhodopsin phosphorylation and may be of relevance for neuronal signalling in the central nervous system. Several alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2012]

HPCAL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPCAL1	NM_002149.4	c.-111+42106A>G		intron_variant		ENST00000307845.8	NP_002140.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPCAL1	ENST00000307845.8	c.-111+42106A>G		intron_variant		1	NM_002149.4	ENSP00000310749.3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77701 AN: 151720 Hom.: 21686 Cov.: 30

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.513 AC: 77821 AN: 151838 Hom.: 21733 Cov.: 30 AF XY: 0.506 AC XY: 37573 AN XY: 74194

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.473

Alfa AF: 0.452 Hom.: 22214

Bravo AF: 0.512

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.44

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: rs10197851; hg19: chr2-10485409;