11-5355046-T-C

Position:

• chr11-5355046-T-C

Variant summary

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

The NM_001005567.3(OR51B5):​c.-359-8136A>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: OR51B5 NM_001005567.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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]

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51B5	NM_001005567.3	c.-359-8136A>G		intron_variant			NP_001005567.2
LOC100418885		n.5355046T>C		intragenic_variant
OR51B5	NR_038321.2	n.85-8136A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*740-9147A>G		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57617 AN: 151812 Hom.: 11168 Cov.: 32

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.: 0 AF XY: 0.473 AC XY: 2944 AN XY: 6226

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome AF: 0.380 AC: 57666 AN: 151930 Hom.: 11182 Cov.: 32 AF XY: 0.375 AC XY: 27871 AN XY: 74250

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.379

Alfa AF: 0.397 Hom.: 3868

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
DANN	Benign	0.60

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: rs2647598; hg19: chr11-5376276;