Variant 6-138412887-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014320.3(HEBP2):c.427G>A(p.Asp143Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0039 in 1,613,006 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 20 hom. )

Consequence

HEBP2
NM_014320.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.77

Variant links:

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]

HEBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01810643).

BP6

Variant 6-138412887-G-A is Benign according to our data. Variant chr6-138412887-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656941.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEBP2	NM_014320.3 linkuse as main transcript	c.427G>A	p.Asp143Asn	missense_variant	4/4	ENST00000607197.6	NP_055135.1	Q9Y5Z4-1
HEBP2	NM_001326380.2 linkuse as main transcript	c.460G>A	p.Asp154Asn	missense_variant	4/4		NP_001313309.1
HEBP2	NM_001326381.2 linkuse as main transcript	c.309G>A	p.Ser103Ser	synonymous_variant	4/4		NP_001313310.1	Q5THN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEBP2	ENST00000607197.6 linkuse as main transcript	c.427G>A	p.Asp143Asn	missense_variant	4/4	1	NM_014320.3	ENSP00000475750.1		Q9Y5Z4-1

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

426

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00456

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00338

AC:

849

AN:

251194

Hom.:

AF XY:

0.00329

AC XY:

447

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00509

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00401

AC:

5864

AN:

1460706

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

2866

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00219

Gnomad4 NFE exome

AF:

0.00457

Gnomad4 OTH exome

AF:

0.00401

GnomAD4 genome

AF:

0.00280

AC:

426

AN:

152300

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00456

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00472

Hom.:

Bravo

AF:

0.00290

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00360

AC:

437

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

HEBP2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.86

M_CAP

Benign

0.0029

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.57

Sift4G

Benign

0.38

Polyphen

0.68

Vest4

0.28

MVP

0.41

MPC

0.072

ClinPred

0.012

GERP RS

5.8

Varity_R

0.56

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over