NM_012378.2:c.483G>C

Variant names:

• chr11-124440603-C-G
• rs74383090
• NM_012378.2:c.483G>C

Variant summary

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

The NM_012378.2(OR8B8):​c.483G>C​(p.Ala161Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00704 in 1,614,070 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (53 hom.)
• Consequence: OR8B8 NM_012378.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.61
• Publications: 4 publications found

Genes affected

OR8B8 (HGNC:8477): (olfactory receptor family 8 subfamily B member 8) 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-124440603-C-G is Benign according to our data. Variant chr11-124440603-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-7.61 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8B8	NM_012378.2	c.483G>C	p.Ala161Ala	synonymous_variant	Exon 3 of 3	ENST00000642064.1	NP_036510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8B8	ENST00000642064.1	c.483G>C	p.Ala161Ala	synonymous_variant	Exon 3 of 3		NM_012378.2	ENSP00000493014.1
OR8B8	ENST00000328064.2	c.483G>C	p.Ala161Ala	synonymous_variant	Exon 1 of 1	6		ENSP00000330280.2

Frequencies

GnomAD3 genomes AF: 0.00502 AC: 763 AN: 152116 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00806

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00500 AC: 1257 AN: 251382 AF XY: 0.00537

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00685

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00397

Gnomad NFE exome AF: 0.00717

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00725 AC: 10598 AN: 1461836 Hom.: 53 Cov.: 32 AF XY: 0.00729 AC XY: 5299 AN XY: 727216

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.00188 AC: 84 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00593 AC: 155 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00538 AC: 464 AN: 86258

European-Finnish (FIN) AF: 0.00406 AC: 217 AN: 53420

Middle Eastern (MID) AF: 0.00537 AC: 31 AN: 5768

European-Non Finnish (NFE) AF: 0.00832 AC: 9248 AN: 1111960

Other (OTH) AF: 0.00609 AC: 368 AN: 60396

GnomAD4 genome AF: 0.00501 AC: 763 AN: 152234 Hom.: 4 Cov.: 32 AF XY: 0.00481 AC XY: 358 AN XY: 74434

African (AFR) AF: 0.00132 AC: 55 AN: 41514

American (AMR) AF: 0.00327 AC: 50 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00395 AC: 19 AN: 4814

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00806 AC: 548 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00474 Hom.: 0

Bravo AF: 0.00471

EpiCase AF: 0.00791

EpiControl AF: 0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR8B8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.058
DANN	Benign	0.37
PhyloP100		-7.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs74383090; hg19: chr11-124310499; COSMIC: COSV60146096;