rs6971999

Positions:

• chr7-143958955-A-G

Variant summary

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

The NM_012369.3(OR2F1):​c.-177A>G variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,196 control chromosomes in the GnomAD database, including 2,704 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 (2704 hom., cov: 30)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: OR2F1 NM_012369.3 splice_region, 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

Genes affected

OR2F1 (HGNC:8246): (olfactory receptor family 2 subfamily F 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. 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, Jun 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2F1	NM_012369.3	c.-177A>G		splice_region_variant, 5_prime_UTR_variant	2/3	ENST00000641412.1	NP_036501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2F1	ENST00000641412.1	c.-177A>G		splice_region_variant, 5_prime_UTR_variant	2/3		NM_012369.3	ENSP00000493004	P1
OR2F1	ENST00000641986.1	n.96A>G		splice_region_variant, non_coding_transcript_exon_variant	2/4
OR2F1	ENST00000470988.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24691 AN: 151074 Hom.: 2694 Cov.: 30

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24758 AN: 151180 Hom.: 2704 Cov.: 30 AF XY: 0.165 AC XY: 12196 AN XY: 73824

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.0990

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.0868

Gnomad4 OTH AF: 0.168

Alfa AF: 0.113 Hom.: 632

Bravo AF: 0.181

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6971999; hg19: chr7-143656048;