chr6-107635075-AGCC-A

Variant names:

• chr6-107635075-AGCC-A
• rs541688197
• NM_018013.4:c.2250_2252delGCC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PM4_Supporting BP6_Very_Strong BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.353
• 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 212281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	NM_018013.4	MANE Select	c.2250_2252delGCC	p.Pro751del	disruptive_inframe_deletion	Exon 6 of 7	NP_060483.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	ENST00000317357.10	TSL:5 MANE Select	c.2250_2252delGCC	p.Pro751del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000318900.5
	SOBP	ENST00000911406.1		c.2250_2252delGCC	p.Pro751del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.2250_2252delGCC	p.Pro751del	disruptive_inframe_deletion	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 615 AN: 149588 Hom.: 2 Cov.: 31

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

GnomAD2 exomes AF: 0.00933 AC: 1260 AN: 135090 AF XY: 0.00871

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 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.: 32 AF XY: 0.00661 AC XY: 4567 AN XY: 691024

African (AFR) AF: 0.00200 AC: 63 AN: 31562

American (AMR) AF: 0.00338 AC: 124 AN: 36684

Ashkenazi Jewish (ASJ) AF: 0.00171 AC: 42 AN: 24510

East Asian (EAS) AF: 0.00125 AC: 45 AN: 35884

South Asian (SAS) AF: 0.00276 AC: 219 AN: 79304

European-Finnish (FIN) AF: 0.00273 AC: 129 AN: 47222

Middle Eastern (MID) AF: 0.00216 AC: 12 AN: 5568

European-Non Finnish (NFE) AF: 0.00792 AC: 8551 AN: 1079652

Other (OTH) AF: 0.00448 AC: 258 AN: 57612

GnomAD4 genome AF: 0.00410 AC: 614 AN: 149690 Hom.: 2 Cov.: 31 AF XY: 0.00363 AC XY: 265 AN XY: 73034

African (AFR) AF: 0.00154 AC: 63 AN: 41018

American (AMR) AF: 0.00159 AC: 24 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.000875 AC: 3 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5032

South Asian (SAS) AF: 0.00105 AC: 5 AN: 4766

European-Finnish (FIN) AF: 0.00131 AC: 13 AN: 9952

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

European-Non Finnish (NFE) AF: 0.00693 AC: 465 AN: 67112

Other (OTH) AF: 0.00288 AC: 6 AN: 2082

Alfa AF: 0.00882 Hom.: 0

Bravo AF: 0.00385

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs541688197; hg19: chr6-107956279; COSMIC: COSV57997167;