16-3204424-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001370640.6(OR1F1):c.178T>C(p.Tyr60His) variant causes a missense change. The variant allele was found at a frequency of 0.00221 in 1,614,134 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: OR1F1 NM_001370640.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.74

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077783763).
• BP6: Variant 16-3204424-T-C is Benign according to our data. Variant chr16-3204424-T-C is described in ClinVar as [Benign]. Clinvar id is 781181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1779/152244) while in subpopulation AFR AF= 0.0409 (1699/41548). AF 95% confidence interval is 0.0393. There are 41 homozygotes in gnomad4. There are 845 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1F1	NM_001370640.6	c.178T>C	p.Tyr60His	missense_variant	4/4	ENST00000304646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1F1	ENST00000304646.3	c.178T>C	p.Tyr60His	missense_variant	4/4		NM_001370640.6	P1
OR1F1	ENST00000576468.1	n.418+13087T>C		intron_variant, non_coding_transcript_variant		3
OR1F1	ENST00000652759.1	n.424-917T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1775 AN: 152126 Hom.: 41 Cov.: 31

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00295 AC: 742 AN: 251486 Hom.: 17 AF XY: 0.00211 AC XY: 287 AN XY: 135918

Gnomad AFR exome AF: 0.0417

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00122 AC: 1787 AN: 1461890 Hom.: 33 Cov.: 33 AF XY: 0.00104 AC XY: 755 AN XY: 727246

Gnomad4 AFR exome AF: 0.0453

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.0117 AC: 1779 AN: 152244 Hom.: 41 Cov.: 31 AF XY: 0.0114 AC XY: 845 AN XY: 74440

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00212 Hom.: 12

Bravo AF: 0.0145

ESP6500AA AF: 0.0385 AC: 169

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00390 AC: 473

Asia WGS AF: 0.000866 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.9	H
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MVP		0.40
MPC		0.0057
ClinPred		0.099	T
GERP RS		5.3
Varity_R		0.89
gMVP		0.29

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: rs61731433; hg19: chr16-3254424; COSMIC: COSV58961888;