rs10946990

Variant names:

• chr6-29428869-T-C
• rs10946990
• NM_001394828.1:c.-92+44A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR11A1	NM_001394828.1	c.-92+44A>G		intron_variant	Intron 4 of 4	ENST00000377149.5	NP_001381757.1
OR11A1	NM_013937.4	c.-91-1137A>G		intron_variant	Intron 1 of 1		NP_039225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR11A1	ENST00000377149.5	c.-92+44A>G		intron_variant	Intron 4 of 4	6	NM_001394828.1	ENSP00000366354.1
OR5V1	ENST00000377154.1	c.-197+2995A>G		intron_variant	Intron 1 of 3	6		ENSP00000366359.1
OR11A1	ENST00000641152.2	c.-91-1137A>G		intron_variant	Intron 1 of 1			ENSP00000493093.1

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

African (AFR) AF: 0.101 AC: 1122 AN: 11092

American (AMR) AF: 0.203 AC: 140 AN: 690

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1261 AN: 3948

East Asian (EAS) AF: 0.247 AC: 624 AN: 2522

South Asian (SAS) AF: 0.108 AC: 1314 AN: 12202

European-Finnish (FIN) AF: 0.276 AC: 59 AN: 214

Middle Eastern (MID) AF: 0.229 AC: 274 AN: 1196

European-Non Finnish (NFE) AF: 0.288 AC: 165848 AN: 575228

Other (OTH) AF: 0.264 AC: 5403 AN: 20460

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

African (AFR) AF: 0.108 AC: 4434 AN: 40918

American (AMR) AF: 0.193 AC: 2928 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3466

East Asian (EAS) AF: 0.228 AC: 1170 AN: 5122

South Asian (SAS) AF: 0.103 AC: 493 AN: 4776

European-Finnish (FIN) AF: 0.290 AC: 2978 AN: 10256

Middle Eastern (MID) AF: 0.217 AC: 62 AN: 286

European-Non Finnish (NFE) AF: 0.283 AC: 19197 AN: 67892

Other (OTH) AF: 0.223 AC: 465 AN: 2086

Alfa AF: 0.229 Hom.: 4598

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
PhyloP100		-2.1
PromoterAI		0.0031	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: rs10946990; hg19: chr6-29396646;