rs369211430

chr6-107634260-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018013.4(SOBP):c.1416C>A(p.Pro472=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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. gnomad4_exome 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 gnomad4_exome. There are 1632 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOBP	NM_018013.4	c.1416C>A	p.Pro472=	synonymous_variant	6/7	ENST00000317357.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOBP	ENST00000317357.10	c.1416C>A	p.Pro472=	synonymous_variant	6/7	5	NM_018013.4	P1

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

GnomAD3 exomes AF: 0.00401 AC: 713 AN: 177888 Hom.: 10 AF XY: 0.00489 AC XY: 482 AN XY: 98514

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 SAS exome AF: 0.0168

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

Gnomad4 AFR exome AF: 0.000216

Gnomad4 AMR exome AF: 0.00111

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0000274

Gnomad4 NFE exome AF: 0.000576

Gnomad4 OTH exome AF: 0.00271

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

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.00331

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

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 14, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

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

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	6.7
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs369211430; hg19: chr6-107955464; COSMIC: COSV57996737; COSMIC: COSV57996737;