2-10390199-G-T

Variant summary

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

The NM_002149.4(HPCAL1):c.-110-6636G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,168 control chromosomes in the GnomAD database, including 3,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.17 (3084 hom., cov: 32)
• Consequence: HPCAL1 NM_002149.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0700

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPCAL1	NM_002149.4	c.-110-6636G>T		intron_variant		ENST00000307845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPCAL1	ENST00000307845.8	c.-110-6636G>T		intron_variant		1	NM_002149.4	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25415 AN: 152050 Hom.: 3084 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0771

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.167 AC: 25431 AN: 152168 Hom.: 3084 Cov.: 32 AF XY: 0.166 AC XY: 12342 AN XY: 74394

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0771

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.148

Alfa AF: 0.104 Hom.: 1199

Bravo AF: 0.187

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vascular endothelial growth factor (VEGF) inhibitor response Other:1

association, no assertion criteria provided

case-control

Department of Ophthalmology, College of Medicine, Hanyang University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.76

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: rs11888704; hg19: chr2-10530325;