Variant 11-5269592-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005330.4(HBE1):c.177C>T(p.Pro59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,613,902 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 11 hom. )

Consequence

HBE1
NM_005330.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.850

Variant links:

Genes affected

HBE1 (HGNC:4830): (hemoglobin subunit epsilon 1) The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains (an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form the embryonic Hb Gower II. Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon - G-gamma - A-gamma - delta - beta-3' [provided by RefSeq, Jul 2008]

HBE1 links:

HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

HBG2 links:

(HGNC:):

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 (BayesDel_noAF=-0.48).

BP6

Variant 11-5269592-G-A is Benign according to our data. Variant chr11-5269592-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037396.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.85 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBE1	NM_005330.4 linkuse as main transcript	c.177C>T	p.Pro59=	synonymous_variant	2/3	ENST00000396895.3	NP_005321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBE1	ENST00000396895.3 linkuse as main transcript	c.177C>T	p.Pro59=	synonymous_variant	2/3	5	NM_005330.4	ENSP00000380104	P1

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00247

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00138

AC:

346

AN:

251174

Hom.:

AF XY:

0.00133

AC XY:

181

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00262

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00241

AC:

3516

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

1721

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000711

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00143

AC:

217

AN:

152242

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00247

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00284

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HBE1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.9

DANN

Benign

0.84

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.0

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

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