rs1974676

chr2-10423787-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.484+699A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,520 control chromosomes in the GnomAD database, including 17,416 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 (17364 hom., cov: 33)
  • Exomes 𝑓: 0.47 (52 hom.)
• Consequence: HPCAL1 NM_002149.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPCAL1	NM_002149.4	c.484+699A>G		intron_variant		ENST00000307845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPCAL1	ENST00000307845.8	c.484+699A>G		intron_variant		1	NM_002149.4	P1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71461 AN: 151998 Hom.: 17354 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.473 AC: 191 AN: 404 Hom.: 52 Cov.: 0 AF XY: 0.505 AC XY: 100 AN XY: 198

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.470 AC: 71520 AN: 152116 Hom.: 17364 Cov.: 33 AF XY: 0.474 AC XY: 35232 AN XY: 74342

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.455

Alfa AF: 0.480 Hom.: 26179

Bravo AF: 0.444

Asia WGS AF: 0.372 AC: 1298 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	0.81
Dann	Benign	0.14

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: rs1974676; hg19: chr2-10563913;