11-5489479-CCTT-C

Position:

• chr11-5489479-CCTT-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_001005163.2(OR52D1):​c.779_781delTCT​(p.Phe260del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 1,614,036 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (11 hom.)
• Consequence: OR52D1 NM_001005163.2 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.422

Genes affected

OR52D1 (HGNC:15212): (olfactory receptor family 52 subfamily D 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. [provided by RefSeq, Jul 2008]

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 Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001005163.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 11-5489479-CCTT-C is Benign according to our data. Variant chr11-5489479-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52D1	NM_001005163.2	c.779_781delTCT	p.Phe260del	disruptive_inframe_deletion	1/1	ENST00000322641.5	NP_001005163.1
OR51B5	NM_001005567.3	c.-360+16087_-360+16089delAAG		intron_variant			NP_001005567.2
OR51B5	NR_038321.2	n.84+16087_84+16089delAAG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52D1	ENST00000322641.5	c.779_781delTCT	p.Phe260del	disruptive_inframe_deletion	1/1	6	NM_001005163.2	ENSP00000326232.5
ENSG00000239920	ENST00000380259.7	n.*739+101343_*739+101345delAAG		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 410 AN: 152176 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00279 AC: 702 AN: 251222 Hom.: 2 AF XY: 0.00278 AC XY: 377 AN XY: 135784

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.000925

Gnomad NFE exome AF: 0.00444

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00370 AC: 5407 AN: 1461742 Hom.: 11 AF XY: 0.00361 AC XY: 2626 AN XY: 727170

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00242

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000812

Gnomad4 FIN exome AF: 0.000974

Gnomad4 NFE exome AF: 0.00432

Gnomad4 OTH exome AF: 0.00369

GnomAD4 genome AF: 0.00269 AC: 410 AN: 152294 Hom.: 3 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74466

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000564

Gnomad4 NFE AF: 0.00416

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00127 Hom.: 2

Bravo AF: 0.00269

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00393

EpiControl AF: 0.00450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

OR52D1: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs561821761; hg19: chr11-5510709;