12-12989352-C-T

Variant names:

• chr12-12989352-C-T
• rs1864190354
• NM_015987.5:c.142G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015987.5(HEBP1):​c.142G>A​(p.Asp48Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D48H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HEBP1 NM_015987.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1321477).

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.142G>A	p.Asp48Asn	missense	Exon 2 of 4	NP_057071.2
	GPRC5D-AS1	NR_149067.1		n.177+9730C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP1	ENST00000014930.9	TSL:1 MANE Select	c.142G>A	p.Asp48Asn	missense	Exon 2 of 4	ENSP00000014930.4	Q9NRV9
	HEBP1	ENST00000905180.1		c.250G>A	p.Asp84Asn	missense	Exon 2 of 4	ENSP00000575238.1
	HEBP1	ENST00000905178.1		c.229G>A	p.Asp77Asn	missense	Exon 2 of 4	ENSP00000575237.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.17
Sift	Benign	0.84	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.53		Gain of catalytic residue at E45 (P = 0.0082)
MVP		0.55
MPC		0.13
ClinPred		0.28	T
GERP RS		6.0
PromoterAI		-0.027	Neutral
Varity_R		0.034
gMVP		0.32
Mutation Taster		=83/17	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: rs1864190354; hg19: chr12-13142286;