dbSNP rs528590496: ODR4:p.Ser268Tyr (chr1-186398335-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017847.6(ODR4):c.803C>A(p.Ser268Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,602,048 control chromosomes in the GnomAD database, including 3 homozygotes. 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. S268F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 3 hom. )

Consequence

ODR4
NM_017847.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55

Publications

0 publications found

Variant links:

Genes affected

ODR4 (HGNC:24299): (odr-4 GPCR localization factor homolog) Predicted to be involved in protein localization. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ODR4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019979179).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017847.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODR4	NM_017847.6	MANE Select	c.803C>A	p.Ser268Tyr	missense	Exon 10 of 14	NP_060317.3
ODR4	NM_001164245.2		c.734C>A	p.Ser245Tyr	missense	Exon 9 of 13	NP_001157717.1	Q5SWX8-2
ODR4	NM_001164246.2		c.707C>A	p.Ser236Tyr	missense	Exon 9 of 13	NP_001157718.1	Q5SWX8-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ODR4	ENST00000287859.11	TSL:1 MANE Select	c.803C>A	p.Ser268Tyr	missense	Exon 10 of 14	ENSP00000287859.6	Q5SWX8-1
ODR4	ENST00000367470.8	TSL:5	c.734C>A	p.Ser245Tyr	missense	Exon 9 of 13	ENSP00000356440.3	Q5SWX8-2
ODR4	ENST00000419367.8	TSL:2	c.707C>A	p.Ser236Tyr	missense	Exon 9 of 13	ENSP00000395084.3	Q5SWX8-4

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

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:

0.00394

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000374

AC:

AN:

243178

AF XY:

0.000477

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000899

Gnomad OTH exome

AF:

0.000341

GnomAD4 exome

AF:

0.000194

AC:

281

AN:

1449802

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

193

AN XY:

721294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33078

American (AMR)

AF:

0.00

AC:

AN:

43220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

39128

South Asian (SAS)

AF:

0.00302

AC:

254

AN:

84196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00000904

AC:

AN:

1105926

Other (OTH)

AF:

0.000285

AC:

AN:

59744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

AF:

0.000125

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00394

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000430

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.036

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.7

PhyloP100

2.6

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.34

Sift

Uncertain

0.019

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.63

MutPred

0.45

Loss of disorder (P = 0.0317)

MVP

0.57

MPC

0.66

ClinPred

0.23

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over