chr1-247451482-C-G

Variant names:

• chr1-247451482-C-G
• rs74154654
• NM_001004492.2:c.501G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004492.2(OR2B11):​c.501G>C​(p.Thr167Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,614,154 control chromosomes in the GnomAD database, including 388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (196 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (192 hom.)
• Consequence: OR2B11 NM_001004492.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.93
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-247451482-C-G is Benign according to our data. Variant chr1-247451482-C-G is described in ClinVar as Benign. ClinVar VariationId is 775700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 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.501G>C	p.Thr167Thr	synonymous	Exon 2 of 2	NP_001004492.1	Q5JQS5
	OR2B11	NR_169840.1		n.1155G>C		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.501G>C	p.Thr167Thr	synonymous	Exon 2 of 2	ENSP00000492892.1	Q5JQS5
	OR2B11	ENST00000641527.1		c.501G>C	p.Thr167Thr	synonymous	Exon 3 of 3	ENSP00000493421.1	Q5JQS5
	OR2B11	ENST00000641613.1		n.1155G>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4023 AN: 152182 Hom.: 194 Cov.: 33

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

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: 0.0144

GnomAD2 exomes AF: 0.00702 AC: 1763 AN: 251176 AF XY: 0.00509

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.00448

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: 0.00286 AC: 4186 AN: 1461854 Hom.: 192 Cov.: 71 AF XY: 0.00247 AC XY: 1798 AN XY: 727226

African (AFR) AF: 0.0956 AC: 3201 AN: 33476

American (AMR) AF: 0.00510 AC: 228 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39694

South Asian (SAS) AF: 0.00157 AC: 135 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.000192 AC: 213 AN: 1111998

Other (OTH) AF: 0.00626 AC: 378 AN: 60394

GnomAD4 genome AF: 0.0265 AC: 4041 AN: 152300 Hom.: 196 Cov.: 33 AF XY: 0.0258 AC XY: 1922 AN XY: 74466

African (AFR) AF: 0.0927 AC: 3851 AN: 41554

American (AMR) AF: 0.00843 AC: 129 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68032

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.00154 Hom.: 4

Bravo AF: 0.0303

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	-0.88
CADD	Benign	0.0080
DANN	Benign	0.53
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs74154654; hg19: chr1-247614784;