NM_018013.4:c.1615A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018013.4(SOBP):c.1615A>G(p.Ile539Val) variant causes a missense change. The variant allele was found at a frequency of 0.00458 in 1,609,272 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 65 hom. )

Consequence

SOBP
NM_018013.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.63

Publications

9 publications found

Variant links:

Genes affected

SOBP (HGNC:29256): (sine oculis binding protein homolog) The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene have also been linked to intellectual disability. [provided by RefSeq, Mar 2011]

SOBP Gene-Disease associations (from GenCC):

intellectual disability, anterior maxillary protrusion, and strabismus
Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
syndromic intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SOBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008447349).

BP6

Variant 6-107634459-A-G is Benign according to our data. Variant chr6-107634459-A-G is described in ClinVar as Benign. ClinVar VariationId is 130360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00609 (919/150884) while in subpopulation SAS AF = 0.0203 (96/4724). AF 95% confidence interval is 0.017. There are 6 homozygotes in GnomAd4. There are 460 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.1615A>G	p.Ile539Val	missense_variant	Exon 6 of 7	ENST00000317357.10	NP_060483.3	A7XYQ1Q24K27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10 link	c.1615A>G	p.Ile539Val	missense_variant	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5		A7XYQ1

Frequencies

GnomAD3 genomes

AF:

0.00611

AC:

921

AN:

150774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0174

Gnomad EAS

AF:

0.00950

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00865

GnomAD2 exomes

AF:

0.00691

AC:

1679

AN:

243044

AF XY:

0.00769

show subpopulations

Gnomad AFR exome

AF:

0.00702

Gnomad AMR exome

AF:

0.00622

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00895

Gnomad FIN exome

AF:

0.000675

Gnomad NFE exome

AF:

0.00341

Gnomad OTH exome

AF:

0.00919

GnomAD4 exome

AF:

0.00442

AC:

6453

AN:

1458388

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

3608

AN XY:

725644

show subpopulations

African (AFR)

AF:

0.00645

AC:

216

AN:

33474

American (AMR)

AF:

0.00662

AC:

296

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

375

AN:

26118

East Asian (EAS)

AF:

0.0147

AC:

585

AN:

39690

South Asian (SAS)

AF:

0.0205

AC:

1768

AN:

86248

European-Finnish (FIN)

AF:

0.000718

AC:

AN:

50172

Middle Eastern (MID)

AF:

0.0276

AC:

159

AN:

5766

European-Non Finnish (NFE)

AF:

0.00233

AC:

2588

AN:

1111850

Other (OTH)

AF:

0.00713

AC:

430

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

422

844

1265

1687

2109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<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:

0.00609

AC:

919

AN:

150884

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

460

AN XY:

73728

show subpopulations

African (AFR)

AF:

0.00730

AC:

299

AN:

40968

American (AMR)

AF:

0.0115

AC:

175

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.0174

AC:

AN:

3456

East Asian (EAS)

AF:

0.00954

AC:

AN:

5034

South Asian (SAS)

AF:

0.0203

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.000192

AC:

AN:

10420

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00319

AC:

216

AN:

67752

Other (OTH)

AF:

0.00856

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00456

Hom.:

Bravo

AF:

0.00638

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00313

AC:

ExAC

AF:

0.00696

AC:

841

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00646

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 30, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

6.6

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.55

REVEL

Benign

0.14

Sift

Uncertain

0.010

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.51

MVP

0.12

ClinPred

0.026

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.14

gMVP

0.54

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over