rs1003653

chr2-10329390-A-Gchr2-10329390-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+26213A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,168 control chromosomes in the GnomAD database, including 2,380 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 0.16 (2380 hom., cov: 33)
• Consequence: HPCAL1 NM_002149.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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 = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPCAL1	NM_002149.4	c.-111+26213A>G		intron_variant		ENST00000307845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPCAL1	ENST00000307845.8	c.-111+26213A>G		intron_variant		1	NM_002149.4	P1
HPCAL1	ENST00000419810.6	c.-450+4994A>G		intron_variant, NMD_transcript_variant		1
HPCAL1	ENST00000381765.7	c.-284+25448A>G		intron_variant		2		P1
HPCAL1	ENST00000423674.5	c.-208+26213A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24101 AN: 152050 Hom.: 2368 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.159 AC: 24148 AN: 152168 Hom.: 2380 Cov.: 33 AF XY: 0.157 AC XY: 11690 AN XY: 74394

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.0761

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.140

Alfa AF: 0.110 Hom.: 1454

Bravo AF: 0.175

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.23
Dann	Benign	0.48

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: rs1003653; hg19: chr2-10469516;