Variant chr19-17226993-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PVS1_StrongBP6_ModerateBS1BS2

The NM_024578.3(OCEL1):c.247-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,574,382 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 14 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 9 hom. )

Consequence

OCEL1
NM_024578.3 splice_acceptor, intron

Scores

Splicing: ADA: 0.9964

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.104

Variant links:

Genes affected

OCEL1 (HGNC:26221): (occludin/ELL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

OCEL1 links:

OCEL1 (HGNC:):

OCEL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.25786164 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.3, offset of 6, new splice context is: gattcctgtggcaactgcAGgga. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant 19-17226993-G-A is Benign according to our data. Variant chr19-17226993-G-A is described in ClinVar as [Benign]. Clinvar id is 717086.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00649 (988/152256) while in subpopulation AFR AF= 0.0223 (925/41550). AF 95% confidence interval is 0.0211. There are 14 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCEL1	NM_024578.3 linkuse as main transcript	c.247-1G>A		splice_acceptor_variant, intron_variant		ENST00000215061.9	NP_078854.1	Q9H607

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCEL1	ENST00000215061.9 linkuse as main transcript	c.247-1G>A		splice_acceptor_variant, intron_variant		1	NM_024578.3	ENSP00000215061.3		Q9H607

Frequencies

GnomAD3 genomes

AF:

0.00648

AC:

986

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00175

AC:

368

AN:

210282

Hom.:

AF XY:

0.00129

AC XY:

149

AN XY:

115430

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000437

Gnomad NFE exome

AF:

0.0000900

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.000721

AC:

1026

AN:

1422126

Hom.:

Cov.:

AF XY:

0.000612

AC XY:

433

AN XY:

707158

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.000324

Gnomad4 NFE exome

AF:

0.0000810

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00649

AC:

988

AN:

152256

Hom.:

Cov.:

AF XY:

0.00617

AC XY:

459

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000317

Hom.:

Bravo

AF:

0.00735

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0218

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00190

AC:

231

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.77

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.10

GERP RS

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.53

SpliceAI score (max)

0.64

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.34

Position offset: 7

DS_AL_spliceai

0.64

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over