5-69492434-G-A

Variant summary

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

The ENST00000355237.6(OCLN):c.-294G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,234 control chromosomes in the GnomAD database, including 55,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.86 (55869 hom., cov: 32)
  • Exomes 𝑓: 0.90 (17 hom.)
• Consequence: OCLN ENST00000355237.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306

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=-0.77).
• BP6: Variant 5-69492434-G-A is Benign according to our data. Variant chr5-69492434-G-A is described in ClinVar as [Benign]. Clinvar id is 1276122.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-69492434-G-A is described in Lovd as [Benign].
• 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCLN	ENST00000355237.6	c.-294G>A		5_prime_UTR_variant	1/9	1		P1
	ENST00000514270.1	n.93+9940C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130125 AN: 152074 Hom.: 55822 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.905 AC: 38 AN: 42 Hom.: 17 Cov.: 0 AF XY: 0.900 AC XY: 27 AN XY: 30

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.867

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.856 AC: 130225 AN: 152192 Hom.: 55869 Cov.: 32 AF XY: 0.855 AC XY: 63639 AN XY: 74410

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.818

Alfa AF: 0.837 Hom.: 44764

Bravo AF: 0.847

Asia WGS AF: 0.882 AC: 3067 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

Sep 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.9
Dann	Benign	0.89

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: rs3733742; hg19: chr5-68788261;