NM_001205254.2:c.51-224T>C

Variant names:

• chr5-69508917-T-C
• rs73116901
• NM_001205254.2:c.51-224T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001205254.2(OCLN):​c.51-224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,242 control chromosomes in the GnomAD database, including 1,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.082 (1694 hom., cov: 33)
• Consequence: OCLN NM_001205254.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.937
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 5-69508917-T-C is Benign according to our data. Variant chr5-69508917-T-C is described in ClinVar as Benign. ClinVar VariationId is 1240479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205254.2. 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_001205254.2	MANE Select	c.51-224T>C		intron	N/A	NP_001192183.1	Q16625-1
	OCLN	NM_001438604.1		c.51-224T>C		intron	N/A	NP_001425533.1
	OCLN	NM_002538.4		c.51-224T>C		intron	N/A	NP_002529.1	Q16625-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCLN	ENST00000396442.7	TSL:1 MANE Select	c.51-224T>C		intron	N/A	ENSP00000379719.2	Q16625-1
	OCLN	ENST00000355237.6	TSL:1	c.51-224T>C		intron	N/A	ENSP00000347379.2	Q16625-1
	OCLN	ENST00000538151.2	TSL:1	c.-25+4623T>C		intron	N/A	ENSP00000445940.1	Q16625-4

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12450 AN: 152124 Hom.: 1688 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.0345

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0635

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

GnomAD4 genome AF: 0.0820 AC: 12478 AN: 152242 Hom.: 1694 Cov.: 33 AF XY: 0.0793 AC XY: 5902 AN XY: 74454

African (AFR) AF: 0.281 AC: 11641 AN: 41496

American (AMR) AF: 0.0323 AC: 494 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 119 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 68030

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0560 Hom.: 140

Bravo AF: 0.0941

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.35
PhyloP100		-0.94
Mutation Taster		=100/0	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: rs73116901; hg19: chr5-68804744;