2-10338810-A-G

Position:

• chr2-10338810-A-G

Variant summary

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

The NM_002149.4(HPCAL1):​c.-111+35633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,068 control chromosomes in the GnomAD database, including 18,195 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 0.47 (18195 hom., cov: 32)
• Consequence: HPCAL1 NM_002149.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPCAL1	NM_002149.4	c.-111+35633A>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+35633A>G		intron_variant		1	NM_002149.4	ENSP00000310749	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70747 AN: 151950 Hom.: 18165 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.466 AC: 70843 AN: 152068 Hom.: 18195 Cov.: 32 AF XY: 0.457 AC XY: 33947 AN XY: 74300

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.434

Alfa AF: 0.407 Hom.: 17881

Bravo AF: 0.469

Asia WGS AF: 0.339 AC: 1182 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	0.59
DANN	Benign	0.29

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: rs4669573; hg19: chr2-10478936;