rs368271940

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018013.4(SOBP):c.1810C>A(p.Gln604Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00138 in 1,563,008 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

SOBP
NM_018013.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 4.56

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014897227).

BP6

Variant 6-107634654-C-A is Benign according to our data. Variant chr6-107634654-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 130358.

BS2

High Homozygotes in GnomAdExome4 at 3 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.1810C>A	p.Gln604Lys	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.1810C>A	p.Gln604Lys	missense_variant	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5		A7XYQ1

Frequencies

GnomAD3 genomes

AF:

0.000857

AC:

130

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00167

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000721

AC:

118

AN:

163742

AF XY:

0.000679

show subpopulations

Gnomad AFR exome

AF:

0.000358

Gnomad AMR exome

AF:

0.0000697

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000264

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.00143

AC:

2025

AN:

1411242

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

950

AN XY:

699346

show subpopulations

African (AFR)

AF:

0.000247

AC:

AN:

32432

American (AMR)

AF:

0.000173

AC:

AN:

40478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

37450

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82560

European-Finnish (FIN)

AF:

0.000279

AC:

AN:

35888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00174

AC:

1905

AN:

1092798

Other (OTH)

AF:

0.00160

AC:

AN:

58668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

134

268

402

536

670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.000857

AC:

130

AN:

151766

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41478

American (AMR)

AF:

0.000197

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000285

AC:

AN:

10524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00167

AC:

113

AN:

67830

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000790

Hom.:

Bravo

AF:

0.000873

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000755

AC:

ExAC

AF:

0.000707

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual disability, anterior maxillary protrusion, and strabismus

Uncertain:1

Jun 19, 2018

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.032

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

4.6

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.92

REVEL

Benign

0.087

Sift

Pathogenic

0.0

Sift4G

Benign

0.91

Polyphen

0.95

Vest4

0.41

MVP

0.040

ClinPred

0.062

GERP RS

3.9

Varity_R

0.27

gMVP

0.44

Mutation Taster

=84/16

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over