chr6-107524274-A-C

Variant names:

• chr6-107524274-A-C
• rs11758333
• NM_018013.4:c.422-9185A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018013.4(SOBP):​c.422-9185A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,068 control chromosomes in the GnomAD database, including 16,847 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (16847 hom., cov: 32)
• Consequence: SOBP NM_018013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

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.422-9185A>C		intron	N/A	NP_060483.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	ENST00000317357.10	TSL:5 MANE Select	c.422-9185A>C		intron	N/A	ENSP00000318900.5
	SOBP	ENST00000477448.1	TSL:5	n.933-9185A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63743 AN: 151950 Hom.: 16843 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63745 AN: 152068 Hom.: 16847 Cov.: 32 AF XY: 0.408 AC XY: 30355 AN XY: 74338

African (AFR) AF: 0.131 AC: 5445 AN: 41510

American (AMR) AF: 0.415 AC: 6342 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.101 AC: 520 AN: 5170

South Asian (SAS) AF: 0.267 AC: 1288 AN: 4826

European-Finnish (FIN) AF: 0.487 AC: 5132 AN: 10548

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41312 AN: 67950

Other (OTH) AF: 0.483 AC: 1021 AN: 2114

Alfa AF: 0.516 Hom.: 10738

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.38
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11758333; hg19: chr6-107845478; COSMIC: COSV58002351;