rs375870689

Variant names:

• chr12-12975388-C-A
• rs375870689
• NM_015987.5:c.490G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-12975388-C-A
• chr12-12975388-C-G
• chr12-12975388-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015987.5(HEBP1):​c.490G>T​(p.Asp164Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,461,154 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D164E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: HEBP1 NM_015987.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 1 publications found

Genes affected

HEBP1 (HGNC:17176): (heme binding protein 1) The full-length protein encoded by this gene is an intracellular tetrapyrrole-binding protein. This protein includes a natural chemoattractant peptide of 21 amino acids at the N-terminus, which is a natural ligand for formyl peptide receptor-like receptor 2 (FPRL2) and promotes calcium mobilization and chemotaxis in monocytes and dendritic cells. [provided by RefSeq, Jul 2008]

GPRC5D-AS1 (HGNC:53599): (GPRC5D and HEBP1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015987.5. 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
	HEBP1	NM_015987.5	MANE Select	c.490G>T	p.Asp164Tyr	missense	Exon 4 of 4	NP_057071.2
	GPRC5D-AS1	NR_149062.1		n.79-4136C>A		intron	N/A
	GPRC5D-AS1	NR_149063.1		n.218-4043C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP1	ENST00000014930.9	TSL:1 MANE Select	c.490G>T	p.Asp164Tyr	missense	Exon 4 of 4	ENSP00000014930.4	Q9NRV9
	HEBP1	ENST00000905180.1		c.598G>T	p.Asp200Tyr	missense	Exon 4 of 4	ENSP00000575238.1
	HEBP1	ENST00000905178.1		c.577G>T	p.Asp193Tyr	missense	Exon 4 of 4	ENSP00000575237.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1461154 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726878

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111608

Other (OTH) AF: 0.0000331 AC: 2 AN: 60352

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.022	D
Polyphen		0.90	P
Vest4		0.66
MutPred		0.51		Gain of catalytic residue at R162 (P = 8e-04)
MVP		0.35
MPC		0.50
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.57
gMVP		0.52
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs375870689; hg19: chr12-13128322;