chr12-48560149-G-A

Variant names:

• chr12-48560149-G-A
• rs17237198
• NM_001396061.1:c.268G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001396061.1(OR5BS1):​c.268G>A​(p.Glu90Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 401,402 control chromosomes in the GnomAD database, including 1,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (532 hom., cov: 32)
  • Exomes 𝑓: 0.084 (958 hom.)
• Consequence: OR5BS1 NM_001396061.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 6 publications found

Genes affected

OR5BS1 (HGNC:19627): (olfactory receptor family 5 subfamily BS member 1 pseudogene) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029495358).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396061.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5BS1	NM_001396061.1	MANE Select	c.268G>A	p.Glu90Lys	missense	Exon 1 of 2	NP_001382990.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5BS1P	ENST00000328207.6	TSL:6 MANE Select	c.268G>A	p.Glu90Lys	missense	Exon 1 of 2	ENSP00000494254.1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12513 AN: 152058 Hom.: 531 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0967

GnomAD4 exome AF: 0.0845 AC: 21056 AN: 249226 Hom.: 958 Cov.: 0 AF XY: 0.0853 AC XY: 10770 AN XY: 126294

African (AFR) AF: 0.0738 AC: 536 AN: 7258

American (AMR) AF: 0.0670 AC: 499 AN: 7446

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 807 AN: 9244

East Asian (EAS) AF: 0.0228 AC: 521 AN: 22894

South Asian (SAS) AF: 0.0483 AC: 151 AN: 3128

European-Finnish (FIN) AF: 0.0870 AC: 1859 AN: 21358

Middle Eastern (MID) AF: 0.148 AC: 432 AN: 2928

European-Non Finnish (NFE) AF: 0.0937 AC: 14838 AN: 158316

Other (OTH) AF: 0.0848 AC: 1413 AN: 16654

GnomAD4 genome AF: 0.0823 AC: 12518 AN: 152176 Hom.: 532 Cov.: 32 AF XY: 0.0800 AC XY: 5947 AN XY: 74378

African (AFR) AF: 0.0720 AC: 2987 AN: 41512

American (AMR) AF: 0.0710 AC: 1086 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 339 AN: 3472

East Asian (EAS) AF: 0.0295 AC: 153 AN: 5178

South Asian (SAS) AF: 0.0560 AC: 269 AN: 4804

European-Finnish (FIN) AF: 0.0846 AC: 896 AN: 10590

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6442 AN: 68008

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0864 Hom.: 450

Bravo AF: 0.0805

TwinsUK AF: 0.0939 AC: 348

ALSPAC AF: 0.0937 AC: 361

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.57
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0029	T
PhyloP100		1.9
GERP RS		4.3
PromoterAI		0.0030	Neutral
gMVP		0.055

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17237198; hg19: chr12-48953932;