rs541688197

chr6-107635075-AGCCGCCGCC-Achr6-107635075-AGCCGCCGCC-AGCCchr6-107635075-AGCCGCCGCC-AGCCGCCchr6-107635075-AGCCGCCGCC-AGCCGCCGCCGCCchr6-107635075-AGCCGCCGCC-AGCCGCCGCCGCCGCCchr6-107635075-AGCCGCCGCC-AGCCGCCGCCGCCGCCGCCchr6-107635075-AGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCchr6-107635075-AGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BP6_Very_Strong

The NM_018013.4(SOBP):c.2244_2252del(p.Pro749_Pro751del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000502 in 1,564,966 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: SOBP NM_018013.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.24

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018013.4.
• BP6: Variant 6-107635075-AGCCGCCGCC-A is Benign according to our data. Variant chr6-107635075-AGCCGCCGCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1336256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOBP	NM_018013.4	c.2244_2252del	p.Pro749_Pro751del	inframe_deletion	6/7	ENST00000317357.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOBP	ENST00000317357.10	c.2244_2252del	p.Pro749_Pro751del	inframe_deletion	6/7	5	NM_018013.4	P1
SOBP	ENST00000494935.1	n.99_107del		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 66 AN: 149604 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000396

Gnomad SAS AF: 0.00314

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000253

Gnomad OTH AF: 0.000485

GnomAD3 exomes AF: 0.00131 AC: 177 AN: 135090 Hom.: 0 AF XY: 0.00153 AC XY: 114 AN XY: 74636

Gnomad AFR exome AF: 0.000791

Gnomad AMR exome AF: 0.000390

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000226

Gnomad SAS exome AF: 0.00483

Gnomad FIN exome AF: 0.00210

Gnomad NFE exome AF: 0.000536

Gnomad OTH exome AF: 0.00112

GnomAD4 exome AF: 0.000508 AC: 719 AN: 1415260 Hom.: 3 AF XY: 0.000608 AC XY: 426 AN XY: 700442

Gnomad4 AFR exome AF: 0.000437

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000109

Gnomad4 SAS exome AF: 0.00330

Gnomad4 FIN exome AF: 0.00177

Gnomad4 NFE exome AF: 0.000260

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.000441 AC: 66 AN: 149706 Hom.: 0 Cov.: 31 AF XY: 0.000452 AC XY: 33 AN XY: 73046

Gnomad4 AFR AF: 0.000341

Gnomad4 AMR AF: 0.000199

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000397

Gnomad4 SAS AF: 0.00315

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.000253

Gnomad4 OTH AF: 0.000480

Alfa AF: 0.000294 Hom.: 0

Bravo AF: 0.000332

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 14, 2019

- -

SOBP-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2022

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). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs541688197; hg19: chr6-107956279;