rs10946990

Positions:

• chr6-29428869-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394828.1(OR11A1):​c.-92+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 778,464 control chromosomes in the GnomAD database, including 29,331 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 0.22 (4090 hom., cov: 29)
  • Exomes 𝑓: 0.28 (25241 hom.)
• Consequence: OR11A1 NM_001394828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

Genes affected

OR11A1 (HGNC:8176): (olfactory receptor family 11 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]

OR5V1 (HGNC:13972): (olfactory receptor family 5 subfamily V 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR11A1	NM_001394828.1	c.-92+44A>G		intron_variant		ENST00000377149.5
OR11A1	NM_013937.4	c.-91-1137A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR11A1	ENST00000377149.5	c.-92+44A>G		intron_variant			NM_001394828.1	P1
OR5V1	ENST00000377154.1	c.-197+2995A>G		intron_variant				P1
OR11A1	ENST00000641152.2	c.-91-1137A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33221 AN: 150828 Hom.: 4091 Cov.: 29

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.281 AC: 176045 AN: 627552 Hom.: 25241 Cov.: 8 AF XY: 0.280 AC XY: 82112 AN XY: 293238

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.220 AC: 33223 AN: 150912 Hom.: 4090 Cov.: 29 AF XY: 0.219 AC XY: 16130 AN XY: 73652

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.223

Alfa AF: 0.250 Hom.: 2141

Bravo AF: 0.207

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs10946990; hg19: chr6-29396646;