Genetic Variant NM_018013.4:c.670-12366G>A (chr6-107621148-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018013.4(SOBP):c.670-12366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 850,542 control chromosomes in the GnomAD database, including 414,078 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.

Frequency

Genomes: 𝑓 0.98 ( 73019 hom., cov: 33)

Exomes 𝑓: 0.99 ( 341059 hom. )

Consequence

SOBP
NM_018013.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.655

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.670-12366G>A		intron_variant	Intron 5 of 6	ENST00000317357.10	NP_060483.3	A7XYQ1Q24K27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10 link	c.670-12366G>A		intron_variant	Intron 5 of 6	5	NM_018013.4	ENSP00000318900.5		A7XYQ1

Frequencies

GnomAD3 genomes

AF:

0.979

AC:

149018

AN:

152238

Hom.:

72960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.955

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.978

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.992

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.968

GnomAD4 exome

AF:

0.988

AC:

690049

AN:

698186

Hom.:

341059

Cov.:

AF XY:

0.988

AC XY:

320803

AN XY:

324582

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.952

AC:

12518

AN:

13150

American (AMR)

AF:

0.983

AC:

792

AN:

806

Ashkenazi Jewish (ASJ)

AF:

0.969

AC:

4244

AN:

4378

East Asian (EAS)

AF:

1.00

AC:

2998

AN:

2998

South Asian (SAS)

AF:

0.993

AC:

13467

AN:

13566

European-Finnish (FIN)

AF:

0.996

AC:

231

AN:

232

Middle Eastern (MID)

AF:

0.955

AC:

1297

AN:

1358

European-Non Finnish (NFE)

AF:

0.989

AC:

632132

AN:

638990

Other (OTH)

AF:

0.985

AC:

22370

AN:

22708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.398

Heterozygous variant carriers

292

584

876

1168

1460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.979

AC:

149136

AN:

152356

Hom.:

73019

Cov.:

AF XY:

0.980

AC XY:

73035

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.955

AC:

39688

AN:

41554

American (AMR)

AF:

0.978

AC:

14966

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

3378

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5193

AN:

5194

South Asian (SAS)

AF:

0.993

AC:

4794

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10624

AN:

10628

Middle Eastern (MID)

AF:

0.956

AC:

281

AN:

294

European-Non Finnish (NFE)

AF:

0.988

AC:

67250

AN:

68048

Other (OTH)

AF:

0.969

AC:

2050

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

161

323

484

646

807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.978

Hom.:

39393

Bravo

AF:

0.976

Asia WGS

AF:

0.993

AC:

3453

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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NM_018013.4:c.670-12366G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over