Genetic Variant HPCAL1:n.*655A>G (chr2-10423787-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000419810.6(HPCAL1):n.*655A>G variant causes a non coding transcript exon 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
ENST00000419810.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.730

Publications

10 publications found

Variant links:

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]

HPCAL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HPCAL1	NM_002149.4 link	c.484+699A>G		intron_variant	Intron 4 of 4	ENST00000307845.8	NP_002140.2	P37235Q6FGY1O75544

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPCAL1	ENST00000307845.8 link	c.484+699A>G		intron_variant	Intron 4 of 4	1	NM_002149.4	ENSP00000310749.3		P37235

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71461

AN:

151998

Hom.:

17354

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.505

AC XY:

100

AN XY:

198

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.265

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.489

AC:

170

AN:

348

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.470

AC:

71520

AN:

152116

Hom.:

17364

Cov.:

AF XY:

0.474

AC XY:

35232

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.464

AC:

19256

AN:

41518

American (AMR)

AF:

0.340

AC:

5190

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1215

AN:

3472

East Asian (EAS)

AF:

0.189

AC:

976

AN:

5176

South Asian (SAS)

AF:

0.548

AC:

2640

AN:

4820

European-Finnish (FIN)

AF:

0.626

AC:

6620

AN:

10580

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34146

AN:

67952

Other (OTH)

AF:

0.455

AC:

961

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1949

3898

5848

7797

9746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.480

Hom.:

36067

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

(source)

DANN

Benign

0.14

PhyloP100

-0.73

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over