Genetic Variant OR4C11:p.Pro260Pro (chr11-55603594-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001004700.3(OR4C11):c.780G>A(p.Pro260Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,346,634 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000026 ( 7 hom. )

Failed GnomAD Quality Control

Consequence

OR4C11
NM_001004700.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.05

Publications

2 publications found

Variant links:

Genes affected

OR4C11 (HGNC:15167): (olfactory receptor family 4 subfamily C member 11) 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]

OR4C11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-55603594-C-T is Benign according to our data. Variant chr11-55603594-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3302846.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.05 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004700.3. 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
	OR4C11	NM_001004700.3	MANE Select	c.780G>A	p.Pro260Pro	synonymous	Exon 4 of 4	NP_001004700.2	Q6IEV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4C11	ENST00000641580.1	MANE Select	c.780G>A	p.Pro260Pro	synonymous	Exon 4 of 4	ENSP00000492971.1	Q6IEV9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

136992

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000219

AC:

AN:

228220

AF XY:

0.0000323

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000105

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:

0.0000260

AC:

AN:

1346634

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

670364

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32820

American (AMR)

AF:

0.000161

AC:

AN:

37316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24368

East Asian (EAS)

AF:

0.00

AC:

AN:

34522

South Asian (SAS)

AF:

0.0000248

AC:

AN:

80536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5016

European-Non Finnish (NFE)

AF:

0.0000165

AC:

AN:

1028220

Other (OTH)

AF:

0.000162

AC:

AN:

55704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

136992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66348

African (AFR)

AF:

0.00

AC:

AN:

39482

American (AMR)

AF:

0.00

AC:

AN:

12388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3178

East Asian (EAS)

AF:

0.00

AC:

AN:

4186

South Asian (SAS)

AF:

0.00

AC:

AN:

4118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61842

Other (OTH)

AF:

0.00

AC:

AN:

1826

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.4

(source)

DANN

Benign

0.47

PhyloP100

-4.0

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over