2-10390199-G-T

Variant names:

• chr2-10390199-G-T
• rs11888704
• NM_002149.4:c.-110-6636G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

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 = 0.318 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL1	NM_002149.4	MANE Select	c.-110-6636G>T		intron	N/A	NP_002140.2
	HPCAL1	NM_001258357.2		c.-110-6636G>T		intron	N/A	NP_001245286.1	P37235
	HPCAL1	NM_001258358.2		c.-110-6636G>T		intron	N/A	NP_001245287.1	P37235

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL1	ENST00000307845.8	TSL:1 MANE Select	c.-110-6636G>T		intron	N/A	ENSP00000310749.3	P37235
	HPCAL1	ENST00000419810.6	TSL:1	n.-283-6636G>T		intron	N/A	ENSP00000416359.2	E9PC71
	HPCAL1	ENST00000904548.1		c.-110-6636G>T		intron	N/A	ENSP00000574607.1

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

African (AFR) AF: 0.315 AC: 13052 AN: 41474

American (AMR) AF: 0.194 AC: 2975 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1710 AN: 5172

South Asian (SAS) AF: 0.0627 AC: 303 AN: 4830

European-Finnish (FIN) AF: 0.0771 AC: 818 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5962 AN: 68000

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.114 Hom.: 2440

Bravo AF: 0.187

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Vascular endothelial growth factor (VEGF) inhibitor response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		0.070
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: rs11888704; hg19: chr2-10530325;