NM_018013.4:c.2250_2252dupGCC

Variant names:

• chr6-107635075-A-AGCC
• rs541688197
• NM_018013.4:c.2250_2252dupGCC

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

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 (★★). Synonymous variant affecting the same amino acid position (i.e. P751P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0052 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (4 hom.)
• Consequence: SOBP NM_018013.4 disruptive_inframe_insertion
• Clinical Significance: 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 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.2250_2252dupGCC	p.Pro751dup	disruptive_inframe_insertion	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.2250_2252dupGCC	p.Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000318900.5
	SOBP	ENST00000911406.1		c.2250_2252dupGCC	p.Pro751dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.2250_2252dupGCC	p.Pro751dup	disruptive_inframe_insertion	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.00523 AC: 782 AN: 149596 Hom.: 3 Cov.: 31

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

GnomAD2 exomes AF: 0.00174 AC: 235 AN: 135090 AF XY: 0.00131

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 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.: 4 Cov.: 33 AF XY: 0.000708 AC XY: 496 AN XY: 700450

African (AFR) AF: 0.0162 AC: 518 AN: 32000

American (AMR) AF: 0.00140 AC: 53 AN: 37754

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25204

East Asian (EAS) AF: 0.000871 AC: 32 AN: 36758

South Asian (SAS) AF: 0.000319 AC: 26 AN: 81556

European-Finnish (FIN) AF: 0.000165 AC: 8 AN: 48540

Middle Eastern (MID) AF: 0.00285 AC: 16 AN: 5618

European-Non Finnish (NFE) AF: 0.000298 AC: 325 AN: 1089294

Other (OTH) AF: 0.00137 AC: 80 AN: 58542

GnomAD4 genome AF: 0.00524 AC: 784 AN: 149698 Hom.: 3 Cov.: 31 AF XY: 0.00505 AC XY: 369 AN XY: 73042

African (AFR) AF: 0.0175 AC: 718 AN: 41012

American (AMR) AF: 0.00172 AC: 26 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: 0.000210 AC: 1 AN: 4766

European-Finnish (FIN) AF: 0.000201 AC: 2 AN: 9956

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

European-Non Finnish (NFE) AF: 0.000417 AC: 28 AN: 67122

Other (OTH) AF: 0.00336 AC: 7 AN: 2082

Alfa AF: 0.000257 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=81/19	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;