rs12434822

Variant names:

• chr14-20229441-T-G
• rs12434822
• ENST00000553765.2:c.40T>G

Variant summary

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

The ENST00000553765.2(OR11H7):​c.40T>G​(p.Leu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 650,184 control chromosomes in the GnomAD database, including 46,902 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 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 0.31 (8991 hom., cov: 32)
  • Exomes 𝑓: 0.38 (37911 hom.)
• Consequence: OR11H7 ENST00000553765.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

OR11H7 (HGNC:15350): (olfactory receptor family 11 subfamily H member 7 (gene/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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR11H7	NR_145509.1	n.461T>G		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR11H7	ENST00000553765.2	c.40T>G	p.Leu14Val	missense_variant	Exon 1 of 1	6		ENSP00000451021.2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47369 AN: 151948 Hom.: 8993 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.342

GnomAD3 exomes AF: 0.365 AC: 34606 AN: 94720 Hom.: 6793 AF XY: 0.374 AC XY: 18251 AN XY: 48810

Gnomad AFR exome AF: 0.0752

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.355

Gnomad SAS exome AF: 0.372

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.383 AC: 191014 AN: 498118 Hom.: 37911 Cov.: 0 AF XY: 0.386 AC XY: 102678 AN XY: 266254

Gnomad4 AFR exome AF: 0.0879

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.311 AC: 47349 AN: 152066 Hom.: 8991 Cov.: 32 AF XY: 0.314 AC XY: 23304 AN XY: 74334

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.338

Alfa AF: 0.394 Hom.: 17884

Bravo AF: 0.297

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Uncertain	0.99

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: rs12434822; hg19: chr14-20697600; COSMIC: COSV59644721;