Genetic Variant HCAR3:c.-141A>G (chr12-122716878-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006018.3(HCAR3):c.-141A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 860,262 control chromosomes in the GnomAD database, including 1 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 0.00036 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

HCAR3
NM_006018.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.569

Publications

1 publications found

Variant links:

Genes affected

HCAR3 (HGNC:16824): (hydroxycarboxylic acid receptor 3) Predicted to enable GTP binding activity and purinergic nucleotide receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

HCAR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCAR3	NM_006018.3 link	c.-141A>G		upstream_gene_variant		ENST00000528880.3	NP_006009.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCAR3	ENST00000528880.3 link	c.-141A>G		upstream_gene_variant		6	NM_006018.3	ENSP00000436714.2

Frequencies

GnomAD3 genomes

AF:

0.000359

AC:

AN:

136560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000570

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000717

Gnomad ASJ

AF:

0.000302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0139

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.00271

GnomAD4 exome

AF:

0.000169

AC:

122

AN:

723630

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

364946

show subpopulations

African (AFR)

AF:

0.000786

AC:

AN:

17816

American (AMR)

AF:

0.000636

AC:

AN:

17308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14228

East Asian (EAS)

AF:

0.0000319

AC:

AN:

31326

South Asian (SAS)

AF:

0.0000239

AC:

AN:

41794

European-Finnish (FIN)

AF:

0.0000456

AC:

AN:

43850

Middle Eastern (MID)

AF:

0.000854

AC:

AN:

3514

European-Non Finnish (NFE)

AF:

0.000158

AC:

AN:

520492

Other (OTH)

AF:

0.000240

AC:

AN:

33302

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

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:

0.000359

AC:

AN:

136632

Hom.:

Cov.:

AF XY:

0.000366

AC XY:

AN XY:

65508

show subpopulations

African (AFR)

AF:

0.000569

AC:

AN:

35176

American (AMR)

AF:

0.000717

AC:

AN:

12560

Ashkenazi Jewish (ASJ)

AF:

0.000302

AC:

AN:

3312

East Asian (EAS)

AF:

0.00

AC:

AN:

4652

South Asian (SAS)

AF:

0.00

AC:

AN:

4284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8474

Middle Eastern (MID)

AF:

0.0150

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

65172

Other (OTH)

AF:

0.00269

AC:

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000248

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.57

PromoterAI

0.34

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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