Genetic Variant NM_024578.3:c.666G>A (chr19-17228303-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024578.3(OCEL1):c.666G>A(p.Lys222Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,584 control chromosomes in the GnomAD database, including 18,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2685 hom., cov: 31)

Exomes 𝑓: 0.14 ( 15744 hom. )

Consequence

OCEL1
NM_024578.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.746

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

Aicardi syndrome
Inheritance: AD Classification: LIMITED Submitted by: Illumina

OCEL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=0.746 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCEL1	NM_024578.3 link	c.666G>A	p.Lys222Lys	synonymous_variant	Exon 5 of 6	ENST00000215061.9	NP_078854.1	Q9H607
OCEL1	XM_006722899.5 link	c.666G>A	p.Lys222Lys	synonymous_variant	Exon 5 of 6		XP_006722962.1
OCEL1	XM_047439441.1 link	c.*46G>A		3_prime_UTR_variant	Exon 4 of 4		XP_047295397.1
OCEL1	XM_047439442.1 link	c.*2G>A		3_prime_UTR_variant	Exon 4 of 4		XP_047295398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCEL1	ENST00000215061.9 link	c.666G>A	p.Lys222Lys	synonymous_variant	Exon 5 of 6	1	NM_024578.3	ENSP00000215061.3		Q9H607

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26158

AN:

151900

Hom.:

2683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.0772

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.174

AC:

43653

AN:

251434

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.274

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.0755

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.135

AC:

197875

AN:

1461566

Hom.:

15744

Cov.:

AF XY:

0.137

AC XY:

99536

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.276

AC:

9246

AN:

33476

American (AMR)

AF:

0.315

AC:

14091

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2752

AN:

26130

East Asian (EAS)

AF:

0.223

AC:

8866

AN:

39696

South Asian (SAS)

AF:

0.220

AC:

18937

AN:

86228

European-Finnish (FIN)

AF:

0.0748

AC:

3993

AN:

53408

Middle Eastern (MID)

AF:

0.169

AC:

974

AN:

5748

European-Non Finnish (NFE)

AF:

0.117

AC:

130160

AN:

1111786

Other (OTH)

AF:

0.147

AC:

8856

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

8300

16601

24901

33202

41502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5098

10196

15294

20392

25490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.172

AC:

26180

AN:

152018

Hom.:

2685

Cov.:

AF XY:

0.172

AC XY:

12780

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.271

AC:

11227

AN:

41458

American (AMR)

AF:

0.229

AC:

3492

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

357

AN:

3472

East Asian (EAS)

AF:

0.237

AC:

1222

AN:

5162

South Asian (SAS)

AF:

0.218

AC:

1048

AN:

4804

European-Finnish (FIN)

AF:

0.0772

AC:

816

AN:

10574

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7587

AN:

67980

Other (OTH)

AF:

0.156

AC:

330

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1049

2098

3147

4196

5245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.141

Hom.:

5414

Bravo

AF:

0.192

Asia WGS

AF:

0.235

AC:

818

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

(source)

DANN

Benign

0.59

PhyloP100

0.75

PromoterAI

0.0015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over