11-5469115-G-A

Position:

• chr11-5469115-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000292896.3(HBE1):​c.-267+36454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 224,600 control chromosomes in the GnomAD database, including 65,424 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 0.76 (43542 hom., cov: 31)
  • Exomes 𝑓: 0.77 (21882 hom.)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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]

OR51A10P (HGNC:15185): (olfactory receptor family 51 subfamily A member 10 pseudogene) 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 (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=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR51B5	NM_001005567.3	c.-360+36454C>T		intron_variant
OR51B5	NR_038321.2	n.84+36454C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR51A10P	ENST00000307165.4	n.308C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114806 AN: 151924 Hom.: 43501 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.771 AC: 55953 AN: 72558 Hom.: 21882 Cov.: 0 AF XY: 0.768 AC XY: 29423 AN XY: 38336

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.773

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.815

Gnomad4 NFE exome AF: 0.785

Gnomad4 OTH exome AF: 0.774

GnomAD4 genome AF: 0.756 AC: 114904 AN: 152042 Hom.: 43542 Cov.: 31 AF XY: 0.755 AC XY: 56123 AN XY: 74318

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.752

Alfa AF: 0.774 Hom.: 90964

Bravo AF: 0.746

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.88

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: rs449937; hg19: chr11-5490345;