chr12-122716961-A-G

Variant names:

• chr12-122716961-A-G
• rs2256572
• NM_006018.3:c.-224T>C

Variant summary

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

The NM_006018.3(HCAR3):​c.-224T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 531,082 control chromosomes in the GnomAD database, including 79,952 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 0.53 (21476 hom., cov: 27)
  • Exomes 𝑓: 0.54 (58476 hom.)
• Consequence: HCAR3 NM_006018.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

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>C		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>C		upstream_gene	N/A	ENSP00000436714.2	P49019

Frequencies

GnomAD3 genomes AF: 0.529 AC: 79455 AN: 150202 Hom.: 21477 Cov.: 27

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.539 AC: 205415 AN: 380764 Hom.: 58476 AF XY: 0.531 AC XY: 104606 AN XY: 197082

African (AFR) AF: 0.498 AC: 5470 AN: 10980

American (AMR) AF: 0.426 AC: 4826 AN: 11322

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 6656 AN: 11362

East Asian (EAS) AF: 0.560 AC: 14537 AN: 25960

South Asian (SAS) AF: 0.332 AC: 9317 AN: 28040

European-Finnish (FIN) AF: 0.503 AC: 16684 AN: 33148

Middle Eastern (MID) AF: 0.531 AC: 857 AN: 1614

European-Non Finnish (NFE) AF: 0.573 AC: 135682 AN: 236680

Other (OTH) AF: 0.526 AC: 11386 AN: 21658

GnomAD4 genome AF: 0.529 AC: 79456 AN: 150318 Hom.: 21476 Cov.: 27 AF XY: 0.520 AC XY: 38020 AN XY: 73140

African (AFR) AF: 0.503 AC: 20538 AN: 40804

American (AMR) AF: 0.470 AC: 7079 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3466

East Asian (EAS) AF: 0.524 AC: 2642 AN: 5038

South Asian (SAS) AF: 0.341 AC: 1636 AN: 4794

European-Finnish (FIN) AF: 0.478 AC: 4790 AN: 10018

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 38992 AN: 67846

Other (OTH) AF: 0.520 AC: 1088 AN: 2092

Alfa AF: 0.447 Hom.: 1341

Bravo AF: 0.532

Asia WGS AF: 0.383 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		2.0
PromoterAI		0.11	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2256572; hg19: chr12-123201508;