12-48560442-G-C

Variant names:

• chr12-48560442-G-C
• rs7312017
• NM_001396061.1:c.561G>C

Variant summary

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

The NM_001396061.1(OR5BS1):​c.561G>C​(p.Leu187Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 401,242 control chromosomes in the GnomAD database, including 47,737 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.

• Frequency:
  • Genomes: 𝑓 0.41 (15206 hom., cov: 31)
  • Exomes 𝑓: 0.50 (32531 hom.)
• Consequence: OR5BS1 NM_001396061.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 7 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=5.4365396E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 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.561G>C	p.Leu187Phe	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.561G>C	p.Leu187Phe	missense	Exon 1 of 2	ENSP00000494254.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62350 AN: 151814 Hom.: 15201 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.498 AC: 124132 AN: 249310 Hom.: 32531 Cov.: 0 AF XY: 0.502 AC XY: 63412 AN XY: 126382

African (AFR) AF: 0.159 AC: 1152 AN: 7254

American (AMR) AF: 0.483 AC: 3592 AN: 7444

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 4668 AN: 9244

East Asian (EAS) AF: 0.259 AC: 5929 AN: 22896

South Asian (SAS) AF: 0.387 AC: 1208 AN: 3120

European-Finnish (FIN) AF: 0.516 AC: 11017 AN: 21344

Middle Eastern (MID) AF: 0.614 AC: 1800 AN: 2930

European-Non Finnish (NFE) AF: 0.549 AC: 87016 AN: 158438

Other (OTH) AF: 0.466 AC: 7750 AN: 16640

GnomAD4 genome AF: 0.411 AC: 62374 AN: 151932 Hom.: 15206 Cov.: 31 AF XY: 0.410 AC XY: 30407 AN XY: 74230

African (AFR) AF: 0.154 AC: 6385 AN: 41444

American (AMR) AF: 0.463 AC: 7078 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3468

East Asian (EAS) AF: 0.190 AC: 977 AN: 5144

South Asian (SAS) AF: 0.383 AC: 1836 AN: 4800

European-Finnish (FIN) AF: 0.523 AC: 5520 AN: 10552

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37245 AN: 67932

Other (OTH) AF: 0.439 AC: 924 AN: 2106

Alfa AF: 0.473 Hom.: 2309

Bravo AF: 0.396

TwinsUK AF: 0.548 AC: 2033

ALSPAC AF: 0.557 AC: 2145

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Benign	0.70
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.00054	T
PhyloP100		-1.1
GERP RS		2.4
gMVP		0.027

Splicing

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

Other links and lift over

dbSNP: rs7312017; hg19: chr12-48954225; COSMIC: COSV60248349;