6-107635075-AGCCGCCGCCGCC-AGCC

Variant names:

• chr6-107635075-AGCCGCCGCC-A
• rs541688197
• NM_018013.4:c.2244_2252delGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_018013.4(SOBP):​c.2244_2252delGCCGCCGCC​(p.Pro749_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 0.000502 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 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.24
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 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 VariationId is 1336256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	NM_018013.4	MANE Select	c.2244_2252delGCCGCCGCC	p.Pro749_Pro751del	disruptive_inframe_deletion	Exon 6 of 7	NP_060483.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	ENST00000317357.10	TSL:5 MANE Select	c.2244_2252delGCCGCCGCC	p.Pro749_Pro751del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000318900.5
	SOBP	ENST00000494935.1	TSL:3	n.99_107delGCCGCCGCC		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.00131 AC: 177 AN: 135090 AF XY: 0.00153

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 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

African (AFR) AF: 0.000437 AC: 14 AN: 32002

American (AMR) AF: 0.000265 AC: 10 AN: 37758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25204

East Asian (EAS) AF: 0.000109 AC: 4 AN: 36758

South Asian (SAS) AF: 0.00330 AC: 269 AN: 81550

European-Finnish (FIN) AF: 0.00177 AC: 86 AN: 48540

Middle Eastern (MID) AF: 0.00392 AC: 22 AN: 5618

European-Non Finnish (NFE) AF: 0.000260 AC: 283 AN: 1089288

Other (OTH) AF: 0.000530 AC: 31 AN: 58542

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

African (AFR) AF: 0.000341 AC: 14 AN: 41020

American (AMR) AF: 0.000199 AC: 3 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.000397 AC: 2 AN: 5032

South Asian (SAS) AF: 0.00315 AC: 15 AN: 4766

European-Finnish (FIN) AF: 0.00141 AC: 14 AN: 9956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000253 AC: 17 AN: 67122

Other (OTH) AF: 0.000480 AC: 1 AN: 2082

Alfa AF: 0.000294 Hom.: 0

Bravo AF: 0.000332

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	SOBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=184/16	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs541688197; hg19: chr6-107956279;