11-58439542-T-C

Variant names:

• chr11-58439542-T-C
• rs144827284
• NM_001004733.3:c.610A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004733.3(OR5B12):​c.610A>G​(p.Asn204Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: OR5B12 NM_001004733.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.278
• Publications: 4 publications found

Genes affected

OR5B12 (HGNC:15432): (olfactory receptor family 5 subfamily B member 12) 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09180918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004733.3. 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
	OR5B12	NM_001004733.3	MANE Select	c.610A>G	p.Asn204Asp	missense	Exon 2 of 2	NP_001004733.1	Q96R08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5B12	ENST00000641921.2	MANE Select	c.610A>G	p.Asn204Asp	missense	Exon 2 of 2	ENSP00000493263.1	Q96R08
	OR5B12	ENST00000302572.2	TSL:6	c.610A>G	p.Asn204Asp	missense	Exon 1 of 1	ENSP00000306657.2	Q96R08

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.000176

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000719 AC: 18 AN: 250280 AF XY: 0.000103

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000725 AC: 106 AN: 1461186 Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61 AN XY: 726918

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.0000225 AC: 1 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86136

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53400

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

European-Non Finnish (NFE) AF: 0.0000854 AC: 95 AN: 1111820

Other (OTH) AF: 0.0000994 AC: 6 AN: 60364

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.0000656 AC: 1 AN: 15254

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68004

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000168 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.033	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.28
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.065
Sift	Benign	0.097	T
Sift4G	Benign	0.14	T
Polyphen		0.35	B
Vest4		0.36
MVP		0.21
MPC		0.042
ClinPred		0.089	T
GERP RS		3.1
Varity_R		0.32
gMVP		0.30
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs144827284; hg19: chr11-58207015;