Genetic Variant HCAR3:c.-224T>G (chr12-122716961-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006018.3(HCAR3):c.-224T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000524 in 381,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 27)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

HCAR3
NM_006018.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006018.3. 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
	HCAR3	NM_006018.3	MANE Select	c.-224T>G		upstream_gene	N/A	NP_006009.2	P49019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCAR3	ENST00000528880.3	TSL:6 MANE Select	c.-224T>G		upstream_gene	N/A	ENSP00000436714.2	P49019

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000524

AC:

AN:

381414

Hom.:

AF XY:

0.0000101

AC XY:

AN XY:

197414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10990

American (AMR)

AF:

0.00

AC:

AN:

11342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11384

East Asian (EAS)

AF:

0.00

AC:

AN:

26030

South Asian (SAS)

AF:

0.00

AC:

AN:

28088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1614

European-Non Finnish (NFE)

AF:

0.00000844

AC:

AN:

237068

Other (OTH)

AF:

0.00

AC:

AN:

21688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

2.0

PromoterAI

0.18

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over