chr16-3204622-G-A

Position:

• chr16-3204622-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370640.6(OR1F1):​c.376G>A​(p.Val126Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,614,032 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.027 (191 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (196 hom.)
• Consequence: OR1F1 NM_001370640.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

Genes affected

OR1F1 (HGNC:8194): (olfactory receptor family 1 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00306952).
• BP6: Variant 16-3204622-G-A is Benign according to our data. Variant chr16-3204622-G-A is described in ClinVar as [Benign]. Clinvar id is 776969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1F1	NM_001370640.6	c.376G>A	p.Val126Met	missense_variant	4/4	ENST00000304646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1F1	ENST00000304646.3	c.376G>A	p.Val126Met	missense_variant	4/4		NM_001370640.6	P1
OR1F1	ENST00000576468.1	n.418+13285G>A		intron_variant, non_coding_transcript_variant		3
OR1F1	ENST00000652759.1	n.424-719G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4165 AN: 152040 Hom.: 190 Cov.: 31

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.00733 AC: 1844 AN: 251486 Hom.: 73 AF XY: 0.00522 AC XY: 710 AN XY: 135916

Gnomad AFR exome AF: 0.0960

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000650

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00325 AC: 4757 AN: 1461874 Hom.: 196 Cov.: 49 AF XY: 0.00285 AC XY: 2072 AN XY: 727238

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00541

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000481

Gnomad4 OTH exome AF: 0.00757

GnomAD4 genome AF: 0.0275 AC: 4178 AN: 152158 Hom.: 191 Cov.: 31 AF XY: 0.0262 AC XY: 1953 AN XY: 74404

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00900 Hom.: 25

Bravo AF: 0.0312

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0915 AC: 402

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00918 AC: 1114

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000711

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	Dec 04, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.29
MVP		0.29
MPC		0.0058
ClinPred		0.085	T
GERP RS		-6.7
Varity_R		0.29
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8045183; hg19: chr16-3254622; COSMIC: COSV58960685;