rs6940398

Variant names:

• chr6-107564799-A-G
• rs6940398
• NM_018013.4:c.574-22281A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018013.4(SOBP):​c.574-22281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,128 control chromosomes in the GnomAD database, including 29,225 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 0.58 (29225 hom., cov: 33)
• Consequence: SOBP NM_018013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4	c.574-22281A>G		intron_variant	Intron 4 of 6	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.574-22281A>G		intron_variant	Intron 4 of 6	5	NM_018013.4	ENSP00000318900.5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88381 AN: 152010 Hom.: 29167 Cov.: 33

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.582 AC: 88492 AN: 152128 Hom.: 29225 Cov.: 33 AF XY: 0.591 AC XY: 43919 AN XY: 74332

African (AFR) AF: 0.870 AC: 36108 AN: 41524

American (AMR) AF: 0.597 AC: 9128 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4649 AN: 5172

South Asian (SAS) AF: 0.730 AC: 3519 AN: 4818

European-Finnish (FIN) AF: 0.475 AC: 5028 AN: 10576

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26930 AN: 67966

Other (OTH) AF: 0.529 AC: 1117 AN: 2110

Alfa AF: 0.458 Hom.: 74022

Bravo AF: 0.601

Asia WGS AF: 0.813 AC: 2823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.70
PhyloP100		0.80
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: rs6940398; hg19: chr6-107886003;