1-158777642-C-A

Position:

• chr1-158777642-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PVS1_Strong BP6_Moderate BS2

The NM_001005278.2(OR6N2):​c.-6-1G>T variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 1,581,004 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (25 hom.)
• Consequence: OR6N2 NM_001005278.2 splice_acceptor, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

Genes affected

OR6N2 (HGNC:15035): (olfactory receptor family 6 subfamily N member 2) 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]

OR6N1 (HGNC:15034): (olfactory receptor family 6 subfamily N 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 Likely_benign. Variant got -2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 3.5838575 fraction of the gene.
• BP6: Variant 1-158777642-C-A is Benign according to our data. Variant chr1-158777642-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6N2	NM_001005278.2	c.-6-1G>T		splice_acceptor_variant, intron_variant		ENST00000641131.1	NP_001005278.1
OR6N1	XM_017000325.2	c.-193-5447G>T		intron_variant			XP_016855814.1
OR6N1	XM_017000326.2	c.-194+3959G>T		intron_variant			XP_016855815.1
OR6N1	XM_017000327.2	c.-193-5447G>T		intron_variant			XP_016855816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6N2	ENST00000641131.1	c.-6-1G>T		splice_acceptor_variant, intron_variant			NM_001005278.2	ENSP00000493148.1

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 557 AN: 152142 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00598

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00399 AC: 938 AN: 235200 Hom.: 3 AF XY: 0.00412 AC XY: 528 AN XY: 128192

Gnomad AFR exome AF: 0.000870

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00926

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00194

Gnomad FIN exome AF: 0.00114

Gnomad NFE exome AF: 0.00644

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00552 AC: 7886 AN: 1428744 Hom.: 25 Cov.: 26 AF XY: 0.00540 AC XY: 3833 AN XY: 709764

Gnomad4 AFR exome AF: 0.000923

Gnomad4 AMR exome AF: 0.00222

Gnomad4 ASJ exome AF: 0.00826

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00643

Gnomad4 OTH exome AF: 0.00523

GnomAD4 genome AF: 0.00366 AC: 557 AN: 152260 Hom.: 1 Cov.: 32 AF XY: 0.00340 AC XY: 253 AN XY: 74454

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00598

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00436 Hom.: 2

Bravo AF: 0.00361

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

OR6N2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	22
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41264044; hg19: chr1-158747432;