11-5355046-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000292896.3(HBE1):c.-266-84890A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,930 control chromosomes in the GnomAD database, including 11,182 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 0.38 ( 11182 hom., cov: 32)

Exomes 𝑓: 0.48 ( 1456 hom. )

Failed GnomAD Quality Control

Consequence

HBE1
ENST00000292896.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

3 publications found

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:

ENSG00000239920 (HGNC:):

ENSG00000239920 links:

OR51B5 (HGNC:19599): (olfactory receptor family 51 subfamily B member 5) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR51B5 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 Gene-Disease associations (from GenCC):

hemoglobinopathy Toms River
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
cyanosis, transient neonatal
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HBG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
LOC100418885		n.5355046T>C	intragenic_variant
OR51B5	NM_001005567.3 link	c.-359-8136A>G	intron_variant	Intron 1 of 4	NP_001005567.2
OR51B5	NR_038321.2 link	n.85-8136A>G	intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7 link	n.*740-9147A>G		intron_variant	Intron 5 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57617

AN:

151812

Hom.:

11168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.374

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.482

AC:

5450

AN:

11316

Hom.:

1456

Cov.:

AF XY:

0.473

AC XY:

2944

AN XY:

6226

show subpopulations

African (AFR)

AF:

0.328

AC:

AN:

250

American (AMR)

AF:

0.326

AC:

AN:

230

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

AN:

152

East Asian (EAS)

AF:

0.101

AC:

AN:

616

South Asian (SAS)

AF:

0.525

AC:

552

AN:

1052

European-Finnish (FIN)

AF:

0.452

AC:

760

AN:

1680

Middle Eastern (MID)

AF:

0.380

AC:

AN:

European-Non Finnish (NFE)

AF:

0.524

AC:

3483

AN:

6644

Other (OTH)

AF:

0.547

AC:

351

AN:

642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

116

233

349

466

582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.380

AC:

57666

AN:

151930

Hom.:

11182

Cov.:

AF XY:

0.375

AC XY:

27871

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.370

AC:

15326

AN:

41432

American (AMR)

AF:

0.369

AC:

5636

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1129

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

788

AN:

5144

South Asian (SAS)

AF:

0.374

AC:

1801

AN:

4816

European-Finnish (FIN)

AF:

0.393

AC:

4151

AN:

10562

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.406

AC:

27611

AN:

67932

Other (OTH)

AF:

0.379

AC:

801

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1826

3651

5477

7302

9128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.395

Hom.:

4785

Bravo

AF:

0.376

Asia WGS

AF:

0.348

AC:

1210

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.6

(source)

DANN

Benign

0.60

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over