rs7314976

Positions:

• chr12-122702353-G-A
• chr12-122702353-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177551.4(HCAR2):​c.931C>T​(p.Arg311Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 149,072 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.097 (2 hom., cov: 32)
  • Exomes 𝑓: 0.052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCAR2 NM_177551.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

Genes affected

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]

ENSG00000256249 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016220659).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCAR2	NM_177551.4	c.931C>T	p.Arg311Cys	missense_variant	1/1	ENST00000328880.6	NP_808219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCAR2	ENST00000328880.6	c.931C>T	p.Arg311Cys	missense_variant	1/1	6	NM_177551.4	ENSP00000375066.2
ENSG00000256249	ENST00000543611.1	n.401+1023G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14536 AN: 148952 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0877

GnomAD3 exomes AF: 0.0389 AC: 8582 AN: 220734 Hom.: 0 AF XY: 0.0378 AC XY: 4505 AN XY: 119176

Gnomad AFR exome AF: 0.00873

Gnomad AMR exome AF: 0.0465

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0218

Gnomad FIN exome AF: 0.0333

Gnomad NFE exome AF: 0.0550

Gnomad OTH exome AF: 0.0552

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0521 AC: 66110 AN: 1268016 Hom.: 0 Cov.: 36 AF XY: 0.0525 AC XY: 33313 AN XY: 634620

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0586

Gnomad4 ASJ exome AF: 0.0638

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0405

Gnomad4 FIN exome AF: 0.0960

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.0615

GnomAD4 genome AF: 0.0975 AC: 14530 AN: 149072 Hom.: 2 Cov.: 32 AF XY: 0.0949 AC XY: 6901 AN XY: 72706

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.115 Hom.: 1

ExAC AF: 0.0811 AC: 9849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.055
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.084	B
Vest4		0.084
MPC		0.99
ClinPred		0.0063	T
GERP RS		3.3
Varity_R		0.079
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7314976; hg19: chr12-123186900; COSMIC: COSV61024824;