Genetic Variant OR8B8:p.Ala161Ala (chr11-124440603-C-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.61

Publications

4 publications found

Variant links:

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]

OR8B8 links:

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ACMG classification

Classification was made for transcript

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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012378.2. 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
	OR8B8	NM_012378.2	MANE Select	c.483G>C	p.Ala161Ala	synonymous	Exon 3 of 3	NP_036510.1	A0A126GW73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8B8	ENST00000642064.1	MANE Select	c.483G>C	p.Ala161Ala	synonymous	Exon 3 of 3	ENSP00000493014.1	Q15620
	OR8B8	ENST00000328064.2	TSL:6	c.483G>C	p.Ala161Ala	synonymous	Exon 1 of 1	ENSP00000330280.2	Q15620

Frequencies

GnomAD3 genomes

AF:

0.00502

AC:

763

AN:

152116

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00729

AC XY:

5299

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33480

American (AMR)

AF:

0.00188

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00593

AC:

155

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

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:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00832

AC:

9248

AN:

1111960

Other (OTH)

AF:

0.00609

AC:

368

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

705

1411

2116

2822

3527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00501

AC:

763

AN:

152234

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

358

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41514

American (AMR)

AF:

0.00327

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00395

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00806

AC:

548

AN:

68022

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00474

Hom.:

Bravo

AF:

0.00471

EpiCase

AF:

0.00791

EpiControl

AF:

0.00747

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.058

(source)

DANN

Benign

0.37

PhyloP100

-7.6

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over