Genetic Variant SOBP:p.Pro751dup (chr6-107635075-A-AGCC) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_018013.4(SOBP):c.2250_2252dupGCC(p.Pro751dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,564,964 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00075 ( 4 hom. )

Consequence

SOBP
NM_018013.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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 -15 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-A-AGCC is Benign according to our data. Variant chr6-107635075-A-AGCC is described in ClinVar as [Benign]. Clinvar id is 716871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00524 (784/149698) while in subpopulation AFR AF= 0.0175 (718/41012). AF 95% confidence interval is 0.0164. There are 3 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.2250_2252dupGCC	p.Pro751dup	disruptive_inframe_insertion	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_2252dupGCC	p.Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5		A7XYQ1
SOBP	ENST00000494935.1 link	n.105_107dupGCC		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00523

AC:

782

AN:

149596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00172

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000396

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000201

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000417

Gnomad OTH

AF:

0.00339

GnomAD3 exomes

AF:

0.00174

AC:

235

AN:

135090

Hom.:

AF XY:

0.00131

AC XY:

AN XY:

74636

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000452

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.000203

Gnomad NFE exome

AF:

0.000610

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.000750

AC:

1061

AN:

1415266

Hom.:

Cov.:

AF XY:

0.000708

AC XY:

496

AN XY:

700450

show subpopulations

Gnomad4 AFR exome

AF:

0.0162

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.000871

Gnomad4 SAS exome

AF:

0.000319

Gnomad4 FIN exome

AF:

0.000165

Gnomad4 NFE exome

AF:

0.000298

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00524

AC:

784

AN:

149698

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

369

AN XY:

73042

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00172

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000397

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.000201

Gnomad4 NFE

AF:

0.000417

Gnomad4 OTH

AF:

0.00336

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 07, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SOBP-related disorder

Benign:1

Oct 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

6-107635075-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCC

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