Genetic Variant NM_018013.4:c.2250_2252delGCC (chr6-107635075-AGCC-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PM4_SupportingBP6_Very_StrongBS2

The NM_018013.4(SOBP):c.2250_2252delGCC(p.Pro751del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 1,547,688 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0068 ( 32 hom. )

Consequence

SOBP
NM_018013.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.353

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_018013.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 6-107635075-AGCC-A is Benign according to our data. Variant chr6-107635075-AGCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 212281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-107635075-AGCC-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.2250_2252delGCC	p.Pro751del	disruptive_inframe_deletion	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.2250_2252delGCC	p.Pro751del	disruptive_inframe_deletion	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5		A7XYQ1
SOBP	ENST00000494935.1 link	n.105_107delGCC		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

615

AN:

149588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.0389

Gnomad AMR

AF:

0.00159

Gnomad ASJ

AF:

0.000875

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.00131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00694

Gnomad OTH

AF:

0.00291

GnomAD3 exomes

AF:

0.00933

AC:

1260

AN:

135090

Hom.:

AF XY:

0.00871

AC XY:

650

AN XY:

74636

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.00546

Gnomad ASJ exome

AF:

0.00330

Gnomad EAS exome

AF:

0.00689

Gnomad SAS exome

AF:

0.00527

Gnomad FIN exome

AF:

0.00399

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00675

AC:

9443

AN:

1397998

Hom.:

AF XY:

0.00661

AC XY:

4567

AN XY:

691024

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.00125

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.00273

Gnomad4 NFE exome

AF:

0.00792

Gnomad4 OTH exome

AF:

0.00448

GnomAD4 genome

AF:

0.00410

AC:

614

AN:

149690

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

265

AN XY:

73034

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00159

Gnomad4 ASJ

AF:

0.000875

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.00131

Gnomad4 NFE

AF:

0.00693

Gnomad4 OTH

AF:

0.00288

Bravo

AF:

0.00385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SOBP: BS2 -

Apr 28, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jan 05, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over