5-69492986-C-T

Position:

• chr5-69492986-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001205254.2(OCLN):​c.-69+86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,010 control chromosomes in the GnomAD database, including 55,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (55631 hom., cov: 27)
  • Exomes 𝑓: 0.86 (178 hom.)
• Consequence: OCLN NM_001205254.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.303

Genes affected

OCLN (HGNC:8104): (occludin) This gene encodes an integral membrane protein that is required for cytokine-induced regulation of the tight junction paracellular permeability barrier. Mutations in this gene are thought to be a cause of band-like calcification with simplified gyration and polymicrogyria (BLC-PMG), an autosomal recessive neurologic disorder that is also known as pseudo-TORCH syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene is present 1.5 Mb downstream on the q arm of chromosome 5. [provided by RefSeq, Apr 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-69492986-C-T is Benign according to our data. Variant chr5-69492986-C-T is described in ClinVar as [Benign]. Clinvar id is 1247058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCLN	NM_001205254.2	c.-69+86C>T		intron_variant		ENST00000396442.7	NP_001192183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCLN	ENST00000396442.7	c.-69+86C>T		intron_variant		1	NM_001205254.2	ENSP00000379719	P1
	ENST00000514270.1	n.93+9388G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 129573 AN: 151404 Hom.: 55584 Cov.: 27

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.857 AC: 418 AN: 488 Hom.: 178 AF XY: 0.865 AC XY: 334 AN XY: 386

Gnomad4 AFR exome AF: 0.786

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.856 AC: 129675 AN: 151522 Hom.: 55631 Cov.: 27 AF XY: 0.855 AC XY: 63311 AN XY: 74012

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.817

Alfa AF: 0.827 Hom.: 2613

Bravo AF: 0.847

Asia WGS AF: 0.881 AC: 3064 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.4
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs28513225; hg19: chr5-68788813;