2-10329390-A-G

Variant names:

• chr2-10329390-A-G
• rs1003653
• NM_002149.4:c.-111+26213A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000298642 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002149.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL1	NM_002149.4	MANE Select	c.-111+26213A>G		intron	N/A	NP_002140.2
	HPCAL1	NM_134421.3		c.-284+25448A>G		intron	N/A	NP_602293.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL1	ENST00000307845.8	TSL:1 MANE Select	c.-111+26213A>G		intron	N/A	ENSP00000310749.3
	HPCAL1	ENST00000419810.6	TSL:1	n.-450+4994A>G		intron	N/A	ENSP00000416359.2
	HPCAL1	ENST00000381765.7	TSL:2	c.-284+25448A>G		intron	N/A	ENSP00000371184.3

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

African (AFR) AF: 0.236 AC: 9776 AN: 41482

American (AMR) AF: 0.200 AC: 3056 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1827 AN: 5172

South Asian (SAS) AF: 0.0761 AC: 367 AN: 4824

European-Finnish (FIN) AF: 0.0953 AC: 1011 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7129 AN: 68000

Other (OTH) AF: 0.140 AC: 295 AN: 2112

Alfa AF: 0.120 Hom.: 2476

Bravo AF: 0.175

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.48
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1003653; hg19: chr2-10469516;