rs754718251

Positions:

• chr6-107634374-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_018013.4(SOBP):​c.1530G>C​(p.Gly510=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,594,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: SOBP NM_018013.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.788

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 -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-107634374-G-C is Benign according to our data. Variant chr6-107634374-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 436827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.788 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOBP	NM_018013.4	c.1530G>C	p.Gly510=	synonymous_variant	6/7	ENST00000317357.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOBP	ENST00000317357.10	c.1530G>C	p.Gly510=	synonymous_variant	6/7	5	NM_018013.4	P1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152046 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000182 AC: 40 AN: 219808 Hom.: 0 AF XY: 0.000124 AC XY: 15 AN XY: 121360

Gnomad AFR exome AF: 0.0000787

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000209

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000355

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.000366 AC: 528 AN: 1442506 Hom.: 0 Cov.: 34 AF XY: 0.000365 AC XY: 262 AN XY: 717494

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000461

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152046 Hom.: 0 Cov.: 31 AF XY: 0.000189 AC XY: 14 AN XY: 74252

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.000166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 03, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.81

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: rs754718251; hg19: chr6-107955578;