rs201438338

Variant names:

• chr19-110893-C-G
• rs201438338
• NM_001005240.3:c.215C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-110893-C-G
• chr19-110893-C-T

Variant summary

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

The NM_001005240.3(OR4F17):​c.215C>G​(p.Pro72Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F17 NM_001005240.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• Publications: 0 publications found

Genes affected

OR4F17 (HGNC:15381): (olfactory receptor family 4 subfamily F member 17) 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=0.23491666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005240.3. 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
	OR4F17	NM_001005240.3	MANE Select	c.215C>G	p.Pro72Arg	missense	Exon 3 of 3	NP_001005240.1	A0A126GWN0
	OR4F17	NM_001429985.1		c.278C>G	p.Pro93Arg	missense	Exon 2 of 2	NP_001416914.1	A0A2U3U062

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4F17	ENST00000585993.3	TSL:6 MANE Select	c.215C>G	p.Pro72Arg	missense	Exon 3 of 3	ENSP00000467301.1	Q8NGA8
	OR4F17	ENST00000618231.3	TSL:6	c.278C>G	p.Pro93Arg	missense	Exon 2 of 2	ENSP00000493422.2	A0A2U3U062
	OR4F17	ENST00000318050.4	TSL:6	c.215C>G	p.Pro72Arg	missense	Exon 1 of 1	ENSP00000315047.3	Q8NGA8

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 403 AN: 143006 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00112

Gnomad AMR AF: 0.00152

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000746

Gnomad FIN AF: 0.00124

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00511

Gnomad OTH AF: 0.00211

GnomAD2 exomes AF: 0.000970 AC: 29 AN: 29898 AF XY: 0.000900

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00116

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00829

Gnomad NFE exome AF: 0.00208

Gnomad OTH exome AF: 0.00101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00472 AC: 6272 AN: 1327816 Hom.: 0 Cov.: 25 AF XY: 0.00453 AC XY: 3018 AN XY: 666294

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000789 AC: 25 AN: 31690

American (AMR) AF: 0.00154 AC: 68 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00224 AC: 57 AN: 25406

East Asian (EAS) AF: 0.0000523 AC: 2 AN: 38228

South Asian (SAS) AF: 0.000669 AC: 55 AN: 82166

European-Finnish (FIN) AF: 0.00224 AC: 119 AN: 53212

Middle Eastern (MID) AF: 0.000761 AC: 3 AN: 3940

European-Non Finnish (NFE) AF: 0.00572 AC: 5687 AN: 993416

Other (OTH) AF: 0.00460 AC: 256 AN: 55602

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00282 AC: 404 AN: 143114 Hom.: 0 Cov.: 25 AF XY: 0.00266 AC XY: 184 AN XY: 69068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000674 AC: 27 AN: 40088

American (AMR) AF: 0.00151 AC: 21 AN: 13866

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 4 AN: 3356

East Asian (EAS) AF: 0.00 AC: 0 AN: 4490

South Asian (SAS) AF: 0.000996 AC: 4 AN: 4016

European-Finnish (FIN) AF: 0.00124 AC: 12 AN: 9684

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00512 AC: 330 AN: 64516

Other (OTH) AF: 0.00209 AC: 4 AN: 1914

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000431 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	5.0	H
PhyloP100		3.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.85
MVP		0.82
MPC		3.5
ClinPred		0.21	T
GERP RS		2.4
PromoterAI		0.017	Neutral
Varity_R		0.78
gMVP		0.18
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201438338; hg19: chr19-110893;