rs872165

chr11-5403302-A-Cchr11-5403302-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

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]

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]

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
OR51B5	NM_001005567.3	c.-359-56392T>G		intron_variant
OR51B5	NR_038321.2	n.85-56392T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR51J1	ENST00000332043.1	n.706A>C		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes AF: 0.116 AC: 17522 AN: 150890 Hom.: 1194 AF XY: 0.115 AC XY: 9297 AN XY: 80856

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 SAS exome AF: 0.114

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

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.0795

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.123

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.154

Alfa AF: 0.121 Hom.: 638

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

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: rs872165; hg19: chr11-5424532; COSMIC: COSV59672817;