12-12995557-T-C

Variant names:

• chr12-12995557-T-C
• rs850942
• NM_015987.5:c.78+4480A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015987.5(HEBP1):​c.78+4480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,104 control chromosomes in the GnomAD database, including 39,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (39809 hom., cov: 31)
• Consequence: HEBP1 NM_015987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

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.78+4480A>G		intron	N/A	NP_057071.2
	GPRC5D-AS1	NR_149067.1		n.177+15935T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP1	ENST00000014930.9	TSL:1 MANE Select	c.78+4480A>G		intron	N/A	ENSP00000014930.4	Q9NRV9
	HEBP1	ENST00000905180.1		c.190+4368A>G		intron	N/A	ENSP00000575238.1
	HEBP1	ENST00000905178.1		c.165+4393A>G		intron	N/A	ENSP00000575237.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105441 AN: 151986 Hom.: 39798 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.716

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.693 AC: 105483 AN: 152104 Hom.: 39809 Cov.: 31 AF XY: 0.699 AC XY: 52011 AN XY: 74360

African (AFR) AF: 0.370 AC: 15323 AN: 41454

American (AMR) AF: 0.777 AC: 11885 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3470

East Asian (EAS) AF: 0.974 AC: 5046 AN: 5180

South Asian (SAS) AF: 0.866 AC: 4169 AN: 4814

European-Finnish (FIN) AF: 0.848 AC: 8971 AN: 10576

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55154 AN: 68006

Other (OTH) AF: 0.718 AC: 1516 AN: 2110

Alfa AF: 0.777 Hom.: 25620

Bravo AF: 0.674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.36
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs850942; hg19: chr12-13148491;