rs6570232

Positions:

• chr6-138408527-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014320.3(HEBP2):​c.419+2376T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,034 control chromosomes in the GnomAD database, including 4,719 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 0.18 (4719 hom., cov: 32)
• Consequence: HEBP2 NM_014320.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

Genes affected

HEBP2 (HGNC:15716): (heme binding protein 2) The protein encoded by this gene is found predominately in the cytoplasm, where it plays a role in the collapse of mitochondrial membrane potential (MMP) prior to necrotic cell death. The encoded protein enhances outer and inner mitochondrial membrane permeabilization, especially under conditions of oxidative stress. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEBP2	NM_014320.3	c.419+2376T>C		intron_variant		ENST00000607197.6	NP_055135.1
HEBP2	NM_001326380.2	c.452+2376T>C		intron_variant			NP_001313309.1
HEBP2	NM_001326381.2	c.301+2494T>C		intron_variant			NP_001313310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEBP2	ENST00000607197.6	c.419+2376T>C		intron_variant		1	NM_014320.3	ENSP00000475750.1
HEBP2	ENST00000448741.5	c.334+2494T>C		intron_variant		5		ENSP00000392101.1
HEBP2	ENST00000367697.7	c.301+2494T>C		intron_variant		2		ENSP00000356670.3
HEBP2	ENST00000453452.1	n.61+2494T>C		intron_variant		3		ENSP00000395958.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27289 AN: 151916 Hom.: 4691 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.180 AC: 27368 AN: 152034 Hom.: 4719 Cov.: 32 AF XY: 0.176 AC XY: 13065 AN XY: 74330

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0968

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.0425

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.181

Alfa AF: 0.136 Hom.: 488

Bravo AF: 0.202

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6570232; hg19: chr6-138729664;