12-12989352-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015987.5(HEBP1):​c.142G>C​(p.Asp48His) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HEBP1 NM_015987.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24027014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEBP1	NM_015987.5	c.142G>C	p.Asp48His	missense_variant	Exon 2 of 4	ENST00000014930.9	NP_057071.2
GPRC5D-AS1	NR_149067.1	n.177+9730C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEBP1	ENST00000014930.9	c.142G>C	p.Asp48His	missense_variant	Exon 2 of 4	1	NM_015987.5	ENSP00000014930.4
HEBP1	ENST00000647702.1	c.196G>C	p.Asp66His	missense_variant	Exon 2 of 4			ENSP00000496930.1
HEBP1	ENST00000536942.1	c.142G>C	p.Asp48His	missense_variant	Exon 2 of 3	2		ENSP00000441678.1
HEBP1	ENST00000535636.1	c.-72G>C		upstream_gene_variant		5		ENSP00000442020.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142G>C (p.D48H) alteration is located in exon 2 (coding exon 2) of the HEBP1 gene. This alteration results from a G to C substitution at nucleotide position 142, causing the aspartic acid (D) at amino acid position 48 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;.;.
Eigen	Benign	0.037
Eigen_PC	Benign	0.077
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.85	D;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N;.;N
REVEL	Benign	0.17
Sift	Benign	0.17	T;.;T
Sift4G	Benign	0.13	T;.;T
Polyphen		0.13	B;.;.
Vest4		0.37
MutPred		0.56		Gain of catalytic residue at E45 (P = 0);.;Gain of catalytic residue at E45 (P = 0);
MVP		0.57
MPC		0.46
ClinPred		0.72	D
GERP RS		6.0
Varity_R		0.051
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-13142286;