Genetic Variant ODR4:c.1000+2105C>G (chr1-186401149-C-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017847.6(ODR4):c.1000+2105C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,595,472 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0058 ( 33 hom. )

Consequence

ODR4
NM_017847.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.924

Publications

7 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011060685).

BP6

Variant 1-186401149-C-G is Benign according to our data. Variant chr1-186401149-C-G is described in ClinVar as Benign. ClinVar VariationId is 715470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 33 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	Effect	Exon Rank	Protein	UniProt
ODR4	NM_017847.6	MANE Select	c.1000+2105C>G	intron	N/A	NP_060317.3
ODR4	NM_001164245.2		c.931+2105C>G	intron	N/A	NP_001157717.1	Q5SWX8-2
ODR4	NM_001164246.2		c.904+2105C>G	intron	N/A	NP_001157718.1	Q5SWX8-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ODR4	ENST00000287859.11	TSL:1 MANE Select	c.1000+2105C>G	intron	N/A	ENSP00000287859.6	Q5SWX8-1
ODR4	ENST00000367470.8	TSL:5	c.931+2105C>G	intron	N/A	ENSP00000356440.3	Q5SWX8-2
ODR4	ENST00000419367.8	TSL:2	c.904+2105C>G	intron	N/A	ENSP00000395084.3	Q5SWX8-4

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

683

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00763

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00472

AC:

1174

AN:

248656

AF XY:

0.00493

show subpopulations

Gnomad AFR exome

AF:

0.000840

Gnomad AMR exome

AF:

0.00494

Gnomad ASJ exome

AF:

0.00647

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.00759

Gnomad OTH exome

AF:

0.00579

GnomAD4 exome

AF:

0.00582

AC:

8402

AN:

1443318

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

4104

AN XY:

717366

show subpopulations

African (AFR)

AF:

0.000936

AC:

AN:

33118

American (AMR)

AF:

0.00501

AC:

221

AN:

44068

Ashkenazi Jewish (ASJ)

AF:

0.00580

AC:

148

AN:

25514

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39204

South Asian (SAS)

AF:

0.000756

AC:

AN:

85970

European-Finnish (FIN)

AF:

0.000783

AC:

AN:

52388

Middle Eastern (MID)

AF:

0.00718

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00687

AC:

7546

AN:

1098210

Other (OTH)

AF:

0.00521

AC:

309

AN:

59278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

382

764

1147

1529

1911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.00448

AC:

681

AN:

152154

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

287

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000891

AC:

AN:

41528

American (AMR)

AF:

0.00569

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00763

AC:

519

AN:

67996

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00678

Hom.:

Bravo

AF:

0.00492

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000834

AC:

ESP6500EA

AF:

0.00774

AC:

ExAC

AF:

0.00479

AC:

578

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.00943

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.29

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.019

M_CAP

Benign

0.0026

MetaRNN

Benign

0.011

PhyloP100

-0.92

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.30

MVP

0.11

MPC

0.62

GERP RS

-1.4

Varity_R

0.050

gMVP

0.074

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over