6-107634459-A-G

Position:

• chr6-107634459-A-G

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.1615A>G​(p.Ile539Val) variant causes a missense change. The variant allele was found at a frequency of 0.00458 in 1,609,272 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0044 (65 hom.)
• Consequence: SOBP NM_018013.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.63

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 (MetaRNN=0.008447349).
• BP6: Variant 6-107634459-A-G is Benign according to our data. Variant chr6-107634459-A-G is described in ClinVar as [Benign]. Clinvar id is 130360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00609 (919/150884) while in subpopulation SAS AF= 0.0203 (96/4724). AF 95% confidence interval is 0.017. There are 6 homozygotes in gnomad4. There are 460 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOBP	NM_018013.4	c.1615A>G	p.Ile539Val	missense_variant	6/7	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.1615A>G	p.Ile539Val	missense_variant	6/7	5	NM_018013.4	ENSP00000318900.5

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 921 AN: 150774 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0174

Gnomad EAS AF: 0.00950

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00865

GnomAD3 exomes AF: 0.00691 AC: 1679 AN: 243044 Hom.: 21 AF XY: 0.00769 AC XY: 1023 AN XY: 133016

Gnomad AFR exome AF: 0.00702

Gnomad AMR exome AF: 0.00622

Gnomad ASJ exome AF: 0.0166

Gnomad EAS exome AF: 0.00895

Gnomad SAS exome AF: 0.0194

Gnomad FIN exome AF: 0.000675

Gnomad NFE exome AF: 0.00341

Gnomad OTH exome AF: 0.00919

GnomAD4 exome AF: 0.00442 AC: 6453 AN: 1458388 Hom.: 65 Cov.: 34 AF XY: 0.00497 AC XY: 3608 AN XY: 725644

Gnomad4 AFR exome AF: 0.00645

Gnomad4 AMR exome AF: 0.00662

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0205

Gnomad4 FIN exome AF: 0.000718

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.00713

GnomAD4 genome AF: 0.00609 AC: 919 AN: 150884 Hom.: 6 Cov.: 31 AF XY: 0.00624 AC XY: 460 AN XY: 73728

Gnomad4 AFR AF: 0.00730

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.0174

Gnomad4 EAS AF: 0.00954

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.000192

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.00856

Alfa AF: 0.00414 Hom.: 4

Bravo AF: 0.00638

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00477 AC: 19

ESP6500EA AF: 0.00313 AC: 26

ExAC AF: 0.00696 AC: 841

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00646

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 30, 2016	- -

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.14
Sift	Uncertain	0.010	D
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.51
MVP		0.12
ClinPred		0.026	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.14
gMVP		0.54

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: rs146747167; hg19: chr6-107955663;