rs3771140

chr2-10404326-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.-25+7406A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,042 control chromosomes in the GnomAD database, including 38,593 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 0.70 (38593 hom., cov: 31)
• Consequence: HPCAL1 NM_002149.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPCAL1	NM_002149.4	c.-25+7406A>T		intron_variant		ENST00000307845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPCAL1	ENST00000307845.8	c.-25+7406A>T		intron_variant		1	NM_002149.4	P1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105878 AN: 151924 Hom.: 38521 Cov.: 31

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.697 AC: 106017 AN: 152042 Hom.: 38593 Cov.: 31 AF XY: 0.700 AC XY: 52007 AN XY: 74316

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.670

Alfa AF: 0.663 Hom.: 4281

Bravo AF: 0.697

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.13
Dann	Benign	0.57

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: rs3771140; hg19: chr2-10544452;