11-5453664-T-C

Position:

• chr11-5453664-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004754.3(OR51I2):​c.176T>C​(p.Met59Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00935 in 1,613,466 control chromosomes in the GnomAD database, including 1,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (634 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (583 hom.)
• Consequence: OR51I2 NM_001004754.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.08

Genes affected

OR51I2 (HGNC:15201): (olfactory receptor family 51 subfamily I member 2) 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025898516).
• BP6: Variant 11-5453664-T-C is Benign according to our data. Variant chr11-5453664-T-C is described in ClinVar as [Benign]. Clinvar id is 1289823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51I2	NM_001004754.3	c.176T>C	p.Met59Thr	missense_variant	2/2	ENST00000641930.1	NP_001004754.1
OR51B5	NM_001005567.3	c.-360+51905A>G		intron_variant			NP_001005567.2
OR51B5	NR_038321.2	n.84+51905A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51I2	ENST00000641930.1	c.176T>C	p.Met59Thr	missense_variant	2/2		NM_001004754.3	ENSP00000493016.1
ENSG00000239920	ENST00000380259.7	n.*740-107765A>G		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7497 AN: 152084 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0129 AC: 3232 AN: 250488 Hom.: 267 AF XY: 0.00928 AC XY: 1256 AN XY: 135318

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.00829

Gnomad ASJ exome AF: 0.00321

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000477

Gnomad OTH exome AF: 0.00720

GnomAD4 exome AF: 0.00517 AC: 7562 AN: 1461264 Hom.: 583 Cov.: 45 AF XY: 0.00443 AC XY: 3221 AN XY: 726892

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.00956

Gnomad4 ASJ exome AF: 0.00334

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000534

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000307

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0494 AC: 7519 AN: 152202 Hom.: 634 Cov.: 32 AF XY: 0.0474 AC XY: 3524 AN XY: 74422

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.00863 Hom.: 142

Bravo AF: 0.0548

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.161 AC: 709

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.0156 AC: 1895

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2020	This variant is associated with the following publications: (PMID: 30924900) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T;T
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.46	.;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.4	.;D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.013	.;D
Polyphen		0.97	D;D
Vest4		0.18
MPC		0.015
ClinPred		0.10	T
GERP RS		5.6
Varity_R		0.84
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs74049540; hg19: chr11-5474894;