11-5403302-A-C

Variant names:

• chr11-5403302-A-C
• rs872165
• ENST00000292896.3:c.-267+102267T>G

Variant summary

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

The ENST00000292896.3(HBE1):​c.-267+102267T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 471,448 control chromosomes in the GnomAD database, including 4,935 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 0.16 (2478 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2457 hom.)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 6 publications found

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]

ENSG00000239920 (HGNC:):

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]

OR51J1 (HGNC:14856): (olfactory receptor family 51 subfamily J member 1) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jan 2017]

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)

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 (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51J1		n.5403302A>C		intragenic_variant
OR51B5	NM_001005567.3	c.-359-56392T>G		intron_variant	Intron 1 of 4		NP_001005567.2
OR51B5	NR_038321.2	n.85-56392T>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*740-57403T>G		intron_variant	Intron 5 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24604 AN: 152004 Hom.: 2479 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.116 AC: 17522 AN: 150890 AF XY: 0.115

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.0783

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.120

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.116 AC: 36930 AN: 319326 Hom.: 2457 Cov.: 0 AF XY: 0.115 AC XY: 20821 AN XY: 180358

African (AFR) AF: 0.292 AC: 2517 AN: 8634

American (AMR) AF: 0.0795 AC: 2169 AN: 27290

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 1554 AN: 10790

East Asian (EAS) AF: 0.134 AC: 1234 AN: 9214

South Asian (SAS) AF: 0.114 AC: 6824 AN: 59742

European-Finnish (FIN) AF: 0.106 AC: 2901 AN: 27266

Middle Eastern (MID) AF: 0.198 AC: 552 AN: 2788

European-Non Finnish (NFE) AF: 0.109 AC: 17393 AN: 159140

Other (OTH) AF: 0.123 AC: 1786 AN: 14462

GnomAD4 genome AF: 0.162 AC: 24605 AN: 152122 Hom.: 2478 Cov.: 33 AF XY: 0.161 AC XY: 12010 AN XY: 74366

African (AFR) AF: 0.291 AC: 12082 AN: 41492

American (AMR) AF: 0.112 AC: 1706 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3472

East Asian (EAS) AF: 0.130 AC: 670 AN: 5168

South Asian (SAS) AF: 0.119 AC: 573 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1310 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7339 AN: 67994

Other (OTH) AF: 0.154 AC: 325 AN: 2112

Alfa AF: 0.123 Hom.: 680

Bravo AF: 0.168

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.65
PhyloP100		-1.6
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: rs872165; hg19: chr11-5424532; COSMIC: COSV59672817;