5-69493132-C-T

Position:

• chr5-69493132-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001205254.2(OCLN):​c.-69+232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 152,186 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.067 (381 hom., cov: 32)
• Consequence: OCLN NM_001205254.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.827

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-69493132-C-T is Benign according to our data. Variant chr5-69493132-C-T is described in ClinVar as [Benign]. Clinvar id is 1174443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCLN	NM_001205254.2	c.-69+232C>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+232C>T		intron_variant		1	NM_001205254.2	ENSP00000379719	P1
	ENST00000514270.1	n.93+9242G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10137 AN: 152070 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0667 AC: 10153 AN: 152186 Hom.: 381 Cov.: 32 AF XY: 0.0686 AC XY: 5107 AN XY: 74404

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0412

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.0265

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0540

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0347 Hom.: 27

Bravo AF: 0.0599

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.1
DANN	Benign	0.87

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: rs112668231; hg19: chr5-68788959;