11-55994411-C-G

Variant names:

• chr11-55994411-C-G
• rs148302675
• NM_003697.1:c.215G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003697.1(OR5F1):​c.215G>C​(p.Cys72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: OR5F1 NM_003697.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.739
• Publications: 1 publications found

Genes affected

OR5F1 (HGNC:8343): (olfactory receptor family 5 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10485062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003697.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5F1	NM_003697.1	MANE Select	c.215G>C	p.Cys72Ser	missense	Exon 1 of 1	NP_003688.1	O95221

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5F1	ENST00000278409.1	TSL:6 MANE Select	c.215G>C	p.Cys72Ser	missense	Exon 1 of 1	ENSP00000278409.1	O95221

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251226 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461658 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 727138

African (AFR) AF: 0.000299 AC: 10 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152034 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74266

African (AFR) AF: 0.000145 AC: 6 AN: 41330

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.6
DANN	Benign	0.45
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.99	L
PhyloP100		0.74
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.18
Sift	Benign	0.23	T
Sift4G	Benign	0.15	T
Polyphen		0.0090	B
Vest4		0.24
MutPred		0.68		Gain of disorder (P = 0.0107)
MVP		0.71
MPC		0.012
ClinPred		0.021	T
GERP RS		3.0
PromoterAI		0.0058	Neutral
Varity_R		0.16
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs148302675; hg19: chr11-55761887;