rs4910755

Variant names:

• chr11-5351521-A-C
• rs4910755
• NM_001004750.1:c.14A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-5351521-A-C
• chr11-5351521-A-G
• chr11-5351521-A-T

Variant summary

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

The NM_001004750.1(OR51B6):​c.14A>C​(p.Lys5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,610,000 control chromosomes in the GnomAD database, including 54,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (5606 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49130 hom.)
• Consequence: OR51B6 NM_001004750.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

Genes affected

OR51B6 (HGNC:19600): (olfactory receptor family 51 subfamily B member 6) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020149052).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51B6	NM_001004750.1	c.14A>C	p.Lys5Thr	missense_variant	Exon 1 of 1	ENST00000380219.1	NP_001004750.1
OR51B5	NM_001005567.3	c.-359-4611T>G		intron_variant	Intron 1 of 4		NP_001005567.2
OR51B5	NR_038321.2	n.85-4611T>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51B6	ENST00000380219.1	c.14A>C	p.Lys5Thr	missense_variant	Exon 1 of 1	6	NM_001004750.1	ENSP00000369568.1
ENSG00000239920	ENST00000380259.7	n.*740-5622T>G		intron_variant	Intron 5 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40282 AN: 151940 Hom.: 5596 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.236 AC: 58466 AN: 247736 Hom.: 7456 AF XY: 0.235 AC XY: 31496 AN XY: 133830

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.0610

Gnomad SAS exome AF: 0.231

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.255 AC: 372458 AN: 1457942 Hom.: 49130 Cov.: 34 AF XY: 0.254 AC XY: 184501 AN XY: 725236

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0554

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.265 AC: 40320 AN: 152058 Hom.: 5606 Cov.: 32 AF XY: 0.263 AC XY: 19529 AN XY: 74336

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0645

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.259

Alfa AF: 0.252 Hom.: 12419

Bravo AF: 0.263

TwinsUK AF: 0.276 AC: 1024

ALSPAC AF: 0.254 AC: 978

ESP6500AA AF: 0.295 AC: 1298

ESP6500EA AF: 0.264 AC: 2268

ExAC AF: 0.239 AC: 28966

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.042
DANN	Benign	0.67
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.013
Sift	Benign	0.58	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.060
MPC		0.0033
ClinPred		0.0010	T
GERP RS		-4.6
Varity_R		0.030
gMVP		0.10

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: rs4910755; hg19: chr11-5372751; COSMIC: COSV66513598; COSMIC: COSV66513598;