11-124440603-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012378.2(OR8B8):​c.483G>A​(p.Ala161Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,614,052 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A161A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.041 (450 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (452 hom.)
• Consequence: OR8B8 NM_012378.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-7.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6287 AN: 152100 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0109 AC: 2730 AN: 251382 AF XY: 0.00797

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.00674

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00450 AC: 6577 AN: 1461834 Hom.: 452 Cov.: 32 AF XY: 0.00382 AC XY: 2779 AN XY: 727214

African (AFR) AF: 0.155 AC: 5198 AN: 33478

American (AMR) AF: 0.00763 AC: 341 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86258

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53420

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5768

European-Non Finnish (NFE) AF: 0.000279 AC: 310 AN: 1111960

Other (OTH) AF: 0.0103 AC: 623 AN: 60396

GnomAD4 genome AF: 0.0414 AC: 6302 AN: 152218 Hom.: 450 Cov.: 32 AF XY: 0.0390 AC XY: 2904 AN XY: 74430

African (AFR) AF: 0.143 AC: 5940 AN: 41498

American (AMR) AF: 0.0168 AC: 257 AN: 15298

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

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

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

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

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68022

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.00239 Hom.: 0

Bravo AF: 0.0482

EpiCase AF: 0.00109

EpiControl AF: 0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.33
DANN	Benign	0.29
PhyloP100		-7.6
Mutation Taster		=100/0	polymorphism (auto)

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;