NM_001002905.2:c.705C>G

Variant names:

• chr11-124250380-C-G
• rs191369801
• NM_001002905.2:c.705C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001002905.2(OR8G1):​c.705C>G​(p.Ser235Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,613,792 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (33 hom.)
• Consequence: OR8G1 NM_001002905.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 1 publications found

Genes affected

OR8G1 (HGNC:8484): (olfactory receptor family 8 subfamily G 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. This family member represents a polymorphic pseudogene, whereby some individuals have a functional allele that encodes a full-length protein, while others have a non-functional allele due to the presence of an early stop codon and a 3' end deletion. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 11-124250380-C-G is Benign according to our data. Variant chr11-124250380-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2642492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002905.2. 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
	OR8G1	NM_001002905.2	MANE Select	c.705C>G	p.Ser235Ser	synonymous	Exon 3 of 3	NP_001002905.1	A0A126GVX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8G1	ENST00000641972.1	MANE Select	c.705C>G	p.Ser235Ser	synonymous	Exon 3 of 3	ENSP00000493289.1	Q15617

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 636 AN: 152100 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00410 AC: 1023 AN: 249360 AF XY: 0.00404

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.00463

Gnomad OTH exome AF: 0.00414

GnomAD4 exome AF: 0.00535 AC: 7826 AN: 1461574 Hom.: 33 Cov.: 60 AF XY: 0.00525 AC XY: 3814 AN XY: 727070

African (AFR) AF: 0.000807 AC: 27 AN: 33468

American (AMR) AF: 0.00141 AC: 63 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00177 AC: 153 AN: 86258

European-Finnish (FIN) AF: 0.0152 AC: 811 AN: 53404

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5756

European-Non Finnish (NFE) AF: 0.00582 AC: 6471 AN: 1111808

Other (OTH) AF: 0.00467 AC: 282 AN: 60370

GnomAD4 genome AF: 0.00418 AC: 636 AN: 152218 Hom.: 2 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74418

African (AFR) AF: 0.00103 AC: 43 AN: 41546

American (AMR) AF: 0.00210 AC: 32 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.0186 AC: 197 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00523 AC: 356 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00487 Hom.: 0

Bravo AF: 0.00294

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs191369801; hg19: chr11-124121127;