1-247451461-C-T

Variant names:

• chr1-247451461-C-T
• rs58058243
• NM_001004492.2:c.522G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001004492.2(OR2B11):​c.522G>A​(p.Gly174Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,614,130 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (201 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (196 hom.)
• Consequence: OR2B11 NM_001004492.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.42
• Publications: 2 publications found

Genes affected

OR2B11 (HGNC:31249): (olfactory receptor family 2 subfamily B member 11) 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-247451461-C-T is Benign according to our data. Variant chr1-247451461-C-T is described in ClinVar as Benign. ClinVar VariationId is 775699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004492.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2B11	NM_001004492.2	MANE Select	c.522G>A	p.Gly174Gly	synonymous	Exon 2 of 2	NP_001004492.1	Q5JQS5
	OR2B11	NR_169840.1		n.1176G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2B11	ENST00000641149.2	MANE Select	c.522G>A	p.Gly174Gly	synonymous	Exon 2 of 2	ENSP00000492892.1	Q5JQS5
	OR2B11	ENST00000641527.1		c.522G>A	p.Gly174Gly	synonymous	Exon 3 of 3	ENSP00000493421.1	Q5JQS5
	OR2B11	ENST00000641613.1		n.1176G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4078 AN: 152184 Hom.: 199 Cov.: 33

Gnomad AFR AF: 0.0940

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00824

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00710 AC: 1783 AN: 251094 AF XY: 0.00518

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00290 AC: 4242 AN: 1461828 Hom.: 196 Cov.: 71 AF XY: 0.00253 AC XY: 1839 AN XY: 727216

African (AFR) AF: 0.0969 AC: 3245 AN: 33476

American (AMR) AF: 0.00517 AC: 231 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.00158 AC: 136 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.000190 AC: 211 AN: 1111988

Other (OTH) AF: 0.00641 AC: 387 AN: 60392

GnomAD4 genome AF: 0.0269 AC: 4094 AN: 152302 Hom.: 201 Cov.: 33 AF XY: 0.0260 AC XY: 1940 AN XY: 74476

African (AFR) AF: 0.0941 AC: 3909 AN: 41550

American (AMR) AF: 0.00823 AC: 126 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68036

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.0159 Hom.: 53

Bravo AF: 0.0308

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.76
PhyloP100		-2.4
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58058243; hg19: chr1-247614763;