rs676823

Positions:

• chr12-122702692-A-G
• chr12-122702692-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_177551.4(HCAR2):​c.592T>C​(p.Phe198Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00044 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCAR2 NM_177551.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011788726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCAR2	NM_177551.4	c.592T>C	p.Phe198Leu	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.592T>C	p.Phe198Leu	missense_variant	1/1		NM_177551.4	ENSP00000375066	P1
	ENST00000543611.1	n.401+1362A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 60 AN: 136962 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000507

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000625

Gnomad SAS AF: 0.000448

Gnomad FIN AF: 0.000526

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000560

Gnomad OTH AF: 0.000535

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000383 AC: 53 AN: 1383966 Hom.: 0 Cov.: 35 AF XY: 0.0000419 AC XY: 29 AN XY: 691390

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000976

Gnomad4 NFE exome AF: 0.0000403

Gnomad4 OTH exome AF: 0.0000863

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000438 AC: 60 AN: 137070 Hom.: 0 Cov.: 31 AF XY: 0.000523 AC XY: 35 AN XY: 66924

Gnomad4 AFR AF: 0.000212

Gnomad4 AMR AF: 0.000506

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000626

Gnomad4 SAS AF: 0.000449

Gnomad4 FIN AF: 0.000526

Gnomad4 NFE AF: 0.000560

Gnomad4 OTH AF: 0.000529

Alfa AF: 0.00207 Hom.: 0

ExAC AF: 0.0000824 AC: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	0.0031	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	2.1e-11	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.29
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.19	B
Vest4		0.099
MutPred		0.16		Loss of helix (P = 0.2022);
MVP		0.54
MPC		0.98
ClinPred		0.17	T
GERP RS		1.2
Varity_R		0.24
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs676823; hg19: chr12-123187239; COSMIC: COSV61024303;