rs16895070

Positions:

• chr6-29553780-T-C

Variant summary

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

The NM_001396058.1(OR2I1P):​c.562T>C​(p.Cys188Arg) variant causes a missense change. The variant allele was found at a frequency of 0.099 in 398,526 control chromosomes in the GnomAD database, including 5,850 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 0.16 (4410 hom., cov: 33)
  • Exomes 𝑓: 0.063 (1440 hom.)
• Consequence: OR2I1P NM_001396058.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60

Genes affected

OR2I1P (HGNC:8258): (olfactory receptor family 2 subfamily I 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016171038).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2I1P	NM_001396058.1	c.562T>C	p.Cys188Arg	missense_variant	2/2	ENST00000641137.2	NP_001382987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2I1P	ENST00000641137.2	c.562T>C	p.Cys188Arg	missense_variant	2/2		NM_001396058.1	ENSP00000493715	P1
OR2I1P	ENST00000641730.1	n.1424T>C		non_coding_transcript_exon_variant	2/2
OR2I1P	ENST00000642037.1	n.750T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23952 AN: 152176 Hom.: 4378 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0627 AC: 15440 AN: 246232 Hom.: 1440 Cov.: 0 AF XY: 0.0595 AC XY: 7423 AN XY: 124782

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.0981

Gnomad4 ASJ exome AF: 0.0896

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.00893

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0907

GnomAD4 genome AF: 0.158 AC: 24029 AN: 152294 Hom.: 4410 Cov.: 33 AF XY: 0.156 AC XY: 11619 AN XY: 74474

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.00960

Gnomad4 NFE AF: 0.0250

Gnomad4 OTH AF: 0.157

Alfa AF: 0.113 Hom.: 478

Bravo AF: 0.181

TwinsUK AF: 0.0183 AC: 68

ALSPAC AF: 0.0189 AC: 73

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Benign	0.89
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0016	T
GERP RS		4.4
gMVP		0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16895070; hg19: chr6-29521557;