11-5154790-T-G

Variant names:

• chr11-5154790-T-G
• rs4910715
• NM_012375.3:c.-665A>C

Variant summary

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

The NM_012375.3(OR52A1):​c.-665A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,856 control chromosomes in the GnomAD database, including 17,536 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 0.48 (17535 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: OR52A1 NM_012375.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 5 publications found

Genes affected

OR52A1 (HGNC:8318): (olfactory receptor family 52 subfamily A member 1) 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012375.3. 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
	OR52A1	NM_012375.3	MANE Select	c.-665A>C		upstream_gene	N/A	NP_036507.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52A1	ENST00000380367.3	TSL:6 MANE Select	c.-665A>C		upstream_gene	N/A	ENSP00000369725.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72729 AN: 151732 Hom.: 17496 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.480 AC: 72821 AN: 151850 Hom.: 17535 Cov.: 31 AF XY: 0.478 AC XY: 35507 AN XY: 74210

African (AFR) AF: 0.496 AC: 20526 AN: 41356

American (AMR) AF: 0.497 AC: 7582 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2075 AN: 5164

South Asian (SAS) AF: 0.549 AC: 2639 AN: 4806

European-Finnish (FIN) AF: 0.424 AC: 4480 AN: 10558

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32558 AN: 67928

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.482 Hom.: 8220

Bravo AF: 0.488

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.76
PhyloP100		-1.3
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4910715; hg19: chr11-5176020; COSMIC: COSV61092584;