NM_012378.2:c.482C>T

Variant names:

• chr11-124440604-G-A
• rs144273608
• NM_012378.2:c.482C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012378.2(OR8B8):​c.482C>T​(p.Ala161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A161A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: OR8B8 NM_012378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.65
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016297996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8B8	NM_012378.2	c.482C>T	p.Ala161Val	missense_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.482C>T	p.Ala161Val	missense_variant	Exon 3 of 3		NM_012378.2	ENSP00000493014.1
OR8B8	ENST00000328064.2	c.482C>T	p.Ala161Val	missense_variant	Exon 1 of 1	6		ENSP00000330280.2

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251382 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461836 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727214

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111960

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74448

African (AFR) AF: 0.000457 AC: 19 AN: 41556

American (AMR) AF: 0.000131 AC: 2 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000257 Hom.: 1

Bravo AF: 0.000121

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482C>T (p.A161V) alteration is located in exon 1 (coding exon 1) of the OR8B8 gene. This alteration results from a C to T substitution at nucleotide position 482, causing the alanine (A) at amino acid position 161 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.016	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.10	N;N
PhyloP100		-1.7
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.022
Sift	Benign	0.15	.;T
Sift4G	Benign	0.24	.;T
Polyphen		0.015	B;B
Vest4		0.034
MVP		0.13
MPC		0.016
ClinPred		0.010	T
GERP RS		0.46
Varity_R		0.035
gMVP		0.15
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: rs144273608; hg19: chr11-124310500;