chr19-111041-A-G

Variant names:

• chr19-111041-A-G
• rs879646758
• NM_001005240.3:c.363A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001005240.3(OR4F17):​c.363A>G​(p.Lys121Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F17 NM_001005240.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.55
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 19-111041-A-G is Benign according to our data. Variant chr19-111041-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3770918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.55 with no splicing effect.

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.363A>G	p.Lys121Lys	synonymous	Exon 3 of 3	NP_001005240.1	A0A126GWN0
	OR4F17	NM_001429985.1		c.426A>G	p.Lys142Lys	synonymous	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.363A>G	p.Lys121Lys	synonymous	Exon 3 of 3	ENSP00000467301.1	Q8NGA8
	OR4F17	ENST00000618231.3	TSL:6	c.426A>G	p.Lys142Lys	synonymous	Exon 2 of 2	ENSP00000493422.2	A0A2U3U062
	OR4F17	ENST00000318050.4	TSL:6	c.363A>G	p.Lys121Lys	synonymous	Exon 1 of 1	ENSP00000315047.3	Q8NGA8

Frequencies

GnomAD3 genomes AF: 0.000895 AC: 130 AN: 145268 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000554

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000210

Gnomad SAS AF: 0.000464

Gnomad FIN AF: 0.00165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00152

GnomAD2 exomes AF: 0.000898 AC: 44 AN: 49002 AF XY: 0.000850

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000293

Gnomad FIN exome AF: 0.00304

Gnomad NFE exome AF: 0.00166

Gnomad OTH exome AF: 0.00287

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000167 AC: 170 AN: 1019998 Hom.: 0 Cov.: 15 AF XY: 0.000168 AC XY: 87 AN XY: 517484

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

African (AFR) AF: 0.0000734 AC: 2 AN: 27242

American (AMR) AF: 0.0000568 AC: 2 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.0000467 AC: 1 AN: 21428

East Asian (EAS) AF: 0.0000850 AC: 3 AN: 35312

South Asian (SAS) AF: 0.0000731 AC: 5 AN: 68426

European-Finnish (FIN) AF: 0.000487 AC: 24 AN: 49316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3204

European-Non Finnish (NFE) AF: 0.000166 AC: 122 AN: 734984

Other (OTH) AF: 0.000245 AC: 11 AN: 44884

⚠️ 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: 0.000894 AC: 130 AN: 145388 Hom.: 0 Cov.: 27 AF XY: 0.000850 AC XY: 60 AN XY: 70598

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

African (AFR) AF: 0.000248 AC: 10 AN: 40340

American (AMR) AF: 0.000553 AC: 8 AN: 14470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4754

South Asian (SAS) AF: 0.000464 AC: 2 AN: 4306

European-Finnish (FIN) AF: 0.00165 AC: 16 AN: 9724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00138 AC: 90 AN: 65232

Other (OTH) AF: 0.00151 AC: 3 AN: 1988

⚠️ 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: 0.00386 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.7
DANN	Benign	0.44
PhyloP100		-2.6
PromoterAI		-0.0058	Neutral
Mutation Taster		=99/1	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: rs879646758; hg19: chr19-111041;