rs508543

Variant names:

• chr1-39688511-A-G
• rs508543
• NM_016257.4:c.-9+2795T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372844.8(HPCAL4):​c.-9+2795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,086 control chromosomes in the GnomAD database, including 10,136 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 0.34 (10136 hom., cov: 32)
• Consequence: HPCAL4 ENST00000372844.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 1 publications found

Genes affected

HPCAL4 (HGNC:18212): (hippocalcin like 4) The protein encoded by this gene is highly similar to human hippocalcin protein and hippocalcin like-1 protein. It also has similarity to rat neural visinin-like Ca2+-binding protein-type 1 and 2 proteins. This encoded protein may be involved in the calcium-dependent regulation of rhodopsin phosphorylation. The transcript of this gene has multiple polyadenylation sites. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372844.8. 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
	HPCAL4	NM_016257.4	MANE Select	c.-9+2795T>C		intron	N/A	NP_057341.1
	HPCAL4	NM_001282396.2		c.-9+2554T>C		intron	N/A	NP_001269325.1
	HPCAL4	NM_001282397.2		c.-9+2795T>C		intron	N/A	NP_001269326.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL4	ENST00000372844.8	TSL:1 MANE Select	c.-9+2795T>C		intron	N/A	ENSP00000361935.3
	HPCAL4	ENST00000617690.2	TSL:5	c.-9+2554T>C		intron	N/A	ENSP00000481834.1
	HPCAL4	ENST00000612703.3	TSL:2	c.-9+2795T>C		intron	N/A	ENSP00000484070.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51798 AN: 151968 Hom.: 10116 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.341 AC: 51837 AN: 152086 Hom.: 10136 Cov.: 32 AF XY: 0.350 AC XY: 26036 AN XY: 74364

African (AFR) AF: 0.251 AC: 10402 AN: 41478

American (AMR) AF: 0.483 AC: 7372 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3472

East Asian (EAS) AF: 0.901 AC: 4670 AN: 5182

South Asian (SAS) AF: 0.516 AC: 2483 AN: 4810

European-Finnish (FIN) AF: 0.295 AC: 3117 AN: 10578

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21062 AN: 67974

Other (OTH) AF: 0.381 AC: 806 AN: 2114

Alfa AF: 0.307 Hom.: 1514

Bravo AF: 0.354

Asia WGS AF: 0.667 AC: 2319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		-0.44
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: rs508543; hg19: chr1-40154183;