rs1028498

Variant names:

• chr6-107653874-C-T
• rs1028498
• NM_018013.4:c.*4-4333C>T

Variant summary

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

The NM_018013.4(SOBP):​c.*4-4333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,024 control chromosomes in the GnomAD database, including 2,826 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 0.14 (2826 hom., cov: 32)
• Consequence: SOBP NM_018013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 2 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4	c.*4-4333C>T		intron_variant	Intron 6 of 6	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.*4-4333C>T		intron_variant	Intron 6 of 6	5	NM_018013.4	ENSP00000318900.5

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20755 AN: 151906 Hom.: 2807 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.137 AC: 20826 AN: 152024 Hom.: 2826 Cov.: 32 AF XY: 0.140 AC XY: 10392 AN XY: 74316

African (AFR) AF: 0.319 AC: 13201 AN: 41426

American (AMR) AF: 0.174 AC: 2665 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1565 AN: 5162

South Asian (SAS) AF: 0.192 AC: 924 AN: 4812

European-Finnish (FIN) AF: 0.0266 AC: 282 AN: 10584

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1798 AN: 67970

Other (OTH) AF: 0.112 AC: 238 AN: 2116

Alfa AF: 0.113 Hom.: 670

Bravo AF: 0.157

Asia WGS AF: 0.250 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		0.12
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: rs1028498; hg19: chr6-107975078;