rs590447

Variant names:

• chr12-122703579-C-T
• rs590447
• ENST00000543611.1:n.401+2249C>T

Variant summary

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

The ENST00000543611.1(ENSG00000256249):​n.401+2249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 151,296 control chromosomes in the GnomAD database, including 520 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 0.058 (520 hom., cov: 30)
• Consequence: ENSG00000256249 ENST00000543611.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 1 publications found

Genes affected

ENSG00000256249 (HGNC:):

HCAR2 (HGNC:24827): (hydroxycarboxylic acid receptor 2) Predicted to enable nicotinic acid receptor activity. Involved in neutrophil apoptotic process and positive regulation of neutrophil apoptotic process. Located in cell junction and plasma membrane. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000543611.1. 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
	HCAR2	NM_177551.4	MANE Select	c.-296G>A		upstream_gene	N/A	NP_808219.1	Q8TDS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000256249	ENST00000543611.1	TSL:4	n.401+2249C>T		intron	N/A
	HCAR2	ENST00000328880.6	TSL:6 MANE Select	c.-296G>A		upstream_gene	N/A	ENSP00000375066.2	Q8TDS4

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8741 AN: 151182 Hom.: 517 Cov.: 30

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.0413

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

GnomAD4 genome AF: 0.0579 AC: 8762 AN: 151296 Hom.: 520 Cov.: 30 AF XY: 0.0570 AC XY: 4216 AN XY: 73918

African (AFR) AF: 0.193 AC: 7868 AN: 40752

American (AMR) AF: 0.0209 AC: 319 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.0467 AC: 224 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00172 AC: 117 AN: 68022

Other (OTH) AF: 0.0408 AC: 86 AN: 2106

Alfa AF: 0.0423 Hom.: 64

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-1.1
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs590447;

hg19: chr12-123188126;