rs369211430

Variant names:

• chr6-107634260-C-A
• rs369211430
• NM_018013.4:c.1416C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018013.4(SOBP):​c.1416C>A​(p.Pro472Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,567,312 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (32 hom.)
• Consequence: SOBP NM_018013.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.606
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 6-107634260-C-A is Benign according to our data. Variant chr6-107634260-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0018 (2541/1415126) while in subpopulation SAS AF = 0.0164 (1355/82450). AF 95% confidence interval is 0.0157. There are 32 homozygotes in GnomAdExome4. There are 1632 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.1416C>A	p.Pro472Pro	synonymous	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.1416C>A	p.Pro472Pro	synonymous	Exon 6 of 7	ENSP00000318900.5

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 185 AN: 152072 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00401 AC: 713 AN: 177888 AF XY: 0.00489

Gnomad AFR exome AF: 0.000108

Gnomad AMR exome AF: 0.00120

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.0000746

Gnomad FIN exome AF: 0.000126

Gnomad NFE exome AF: 0.00131

Gnomad OTH exome AF: 0.00478

GnomAD4 exome AF: 0.00180 AC: 2541 AN: 1415126 Hom.: 32 Cov.: 33 AF XY: 0.00233 AC XY: 1632 AN XY: 701788

African (AFR) AF: 0.000216 AC: 7 AN: 32374

American (AMR) AF: 0.00111 AC: 46 AN: 41580

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 282 AN: 25590

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37162

South Asian (SAS) AF: 0.0164 AC: 1355 AN: 82450

European-Finnish (FIN) AF: 0.0000274 AC: 1 AN: 36478

Middle Eastern (MID) AF: 0.0104 AC: 58 AN: 5554

European-Non Finnish (NFE) AF: 0.000576 AC: 631 AN: 1094984

Other (OTH) AF: 0.00271 AC: 160 AN: 58954

GnomAD4 genome AF: 0.00122 AC: 185 AN: 152186 Hom.: 4 Cov.: 31 AF XY: 0.00134 AC XY: 100 AN XY: 74404

African (AFR) AF: 0.0000962 AC: 4 AN: 41568

American (AMR) AF: 0.000981 AC: 15 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5132

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 67964

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00269 Hom.: 1

Bravo AF: 0.00104

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 14, 2015

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Intellectual disability, anterior maxillary protrusion, and strabismus Benign:1

Jul 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.7
DANN	Benign	0.86
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs369211430; hg19: chr6-107955464; COSMIC: COSV57996737; COSMIC: COSV57996737;