rs3733742

Variant names:

• chr5-69492434-G-A
• rs3733742
• ENST00000355237.6:c.-294G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306
• Publications: 6 publications found

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]

OCLN Gene-Disease associations (from GenCC):

• pseudo-TORCH syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• pseudo-TORCH syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000249295 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1276122.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355237.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCLN	NM_001438604.1		c.-345G>A		upstream_gene	N/A	NP_001425533.1
	OCLN	NM_002538.4		c.-294G>A		upstream_gene	N/A	NP_002529.1	Q16625-1
	OCLN	NM_001410743.1		c.-294G>A		upstream_gene	N/A	NP_001397672.1	Q16625-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCLN	ENST00000355237.6	TSL:1	c.-294G>A		5_prime_UTR	Exon 1 of 9	ENSP00000347379.2	Q16625-1
	OCLN	ENST00000901826.1		c.-294G>A		5_prime_UTR	Exon 1 of 8	ENSP00000571885.1
	ENSG00000249295	ENST00000514270.1	TSL:5	n.93+9940C>T		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.867 AC: 26 AN: 30

Other (OTH) AF: 1.00 AC: 6 AN: 6

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

African (AFR) AF: 0.890 AC: 36990 AN: 41554

American (AMR) AF: 0.752 AC: 11515 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4301 AN: 5118

South Asian (SAS) AF: 0.895 AC: 4312 AN: 4820

European-Finnish (FIN) AF: 0.891 AC: 9461 AN: 10618

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.858 AC: 58308 AN: 67988

Other (OTH) AF: 0.818 AC: 1727 AN: 2112

Alfa AF: 0.842 Hom.: 77103

Bravo AF: 0.847

Asia WGS AF: 0.882 AC: 3067 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.89
PhyloP100		-0.31
PromoterAI		-0.11	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3733742; hg19: chr5-68788261;