Genetic Variant NM_017847.6:c.1126G>A (chr1-186406208-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_017847.6(ODR4):c.1126G>A(p.Glu376Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000601 in 1,611,400 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

ODR4
NM_017847.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

Publications

8 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20984805).

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.1126G>A	p.Glu376Lys	missense	Exon 12 of 14	NP_060317.3
ODR4	NM_001164245.2		c.1057G>A	p.Glu353Lys	missense	Exon 11 of 13	NP_001157717.1	Q5SWX8-2
ODR4	NM_001164246.2		c.1030G>A	p.Glu344Lys	missense	Exon 11 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.1126G>A	p.Glu376Lys	missense	Exon 12 of 14	ENSP00000287859.6	Q5SWX8-1
ODR4	ENST00000367470.8	TSL:5	c.1057G>A	p.Glu353Lys	missense	Exon 11 of 13	ENSP00000356440.3	Q5SWX8-2
ODR4	ENST00000419367.8	TSL:2	c.1030G>A	p.Glu344Lys	missense	Exon 11 of 13	ENSP00000395084.3	Q5SWX8-4

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000587

AC:

145

AN:

246878

AF XY:

0.000612

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000238

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000872

Gnomad OTH exome

AF:

0.000673

GnomAD4 exome

AF:

0.000603

AC:

880

AN:

1459130

Hom.:

Cov.:

AF XY:

0.000599

AC XY:

435

AN XY:

725844

show subpopulations

African (AFR)

AF:

0.0000899

AC:

AN:

33366

American (AMR)

AF:

0.000225

AC:

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.00276

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39484

South Asian (SAS)

AF:

0.00

AC:

AN:

85778

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000681

AC:

756

AN:

1110728

Other (OTH)

AF:

0.000597

AC:

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000578

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41546

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000911

AC:

AN:

68024

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000877

Hom.:

Bravo

AF:

0.000646

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000270

AC:

ESP6500EA

AF:

0.000731

AC:

ExAC

AF:

0.000604

AC:

EpiCase

AF:

0.00121

EpiControl

AF:

0.00131

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.026

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.7

PhyloP100

6.7

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.91

MVP

0.48

MPC

0.62

ClinPred

0.11

GERP RS

5.4

Varity_R

0.72

gMVP

0.71

Mutation Taster

=75/25

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

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