19-15087724-G-A

Position:

• chr19-15087724-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001004713.2(OR1I1):​c.659G>A​(p.Arg220His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,614,114 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 34)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: OR1I1 NM_001004713.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

Genes affected

OR1I1 (HGNC:8207): (olfactory receptor family 1 subfamily I 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035028458).
• BP6: Variant 19-15087724-G-A is Benign according to our data. Variant chr19-15087724-G-A is described in ClinVar as [Benign]. Clinvar id is 777448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1812/152300) while in subpopulation AFR AF= 0.0417 (1734/41552). AF 95% confidence interval is 0.0401. There are 32 homozygotes in gnomad4. There are 871 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1I1	NM_001004713.2	c.659G>A	p.Arg220His	missense_variant	2/2	ENST00000641398.1	NP_001004713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1I1	ENST00000641398.1	c.659G>A	p.Arg220His	missense_variant	2/2		NM_001004713.2	ENSP00000493393.1
OR1I1	ENST00000209540.2	c.659G>A	p.Arg220His	missense_variant	1/1	6		ENSP00000209540.2

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1805 AN: 152182 Hom.: 32 Cov.: 34

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00318 AC: 797 AN: 250860 Hom.: 12 AF XY: 0.00234 AC XY: 317 AN XY: 135566

Gnomad AFR exome AF: 0.0428

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00121 AC: 1767 AN: 1461814 Hom.: 35 Cov.: 62 AF XY: 0.00103 AC XY: 748 AN XY: 727204

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000656

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.0119 AC: 1812 AN: 152300 Hom.: 32 Cov.: 34 AF XY: 0.0117 AC XY: 871 AN XY: 74474

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00201 Hom.: 12

Bravo AF: 0.0137

ESP6500AA AF: 0.0468 AC: 206

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00390 AC: 473

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.20
DEOGEN2	Benign	0.0080	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.089	.;T
MetaRNN	Benign	0.0035	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.54	N;N
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.74	.;N
REVEL	Benign	0.027
Sift	Benign	0.67	.;T
Sift4G	Benign	0.58	.;T
Polyphen		0.14	B;B
Vest4		0.086
MVP		0.15
MPC		0.27
ClinPred		0.0059	T
GERP RS		-0.087
Varity_R		0.054
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs115448158; hg19: chr19-15198535;