Genetic Variant OTX1:p.Leu264Leu (chr2-63056043-C-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014562.4(OTX1):c.792C>G(p.Leu264Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,932 control chromosomes in the GnomAD database, including 15,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1394 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13892 hom. )

Consequence

OTX1
NM_014562.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0240

Publications

10 publications found

Variant links:

Genes affected

OTX1 (HGNC:8521): (orthodenticle homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. A similar protein in mouse is required for proper brain and sensory organ development and can cause epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

OTX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-63056043-C-G is Benign according to our data. Variant chr2-63056043-C-G is described in ClinVar as Benign. ClinVar VariationId is 1241607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.024 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014562.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTX1	NM_014562.4	MANE Select	c.792C>G	p.Leu264Leu	synonymous	Exon 5 of 5	NP_055377.1	P32242
OTX1	NM_001199770.2		c.792C>G	p.Leu264Leu	synonymous	Exon 5 of 5	NP_001186699.1	P32242
OTX1	NR_130153.2		n.1155C>G		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTX1	ENST00000282549.7	TSL:1 MANE Select	c.792C>G	p.Leu264Leu	synonymous	Exon 5 of 5	ENSP00000282549.2	P32242
OTX1	ENST00000366671.7	TSL:3	c.792C>G	p.Leu264Leu	synonymous	Exon 5 of 5	ENSP00000355631.3	P32242
OTX1	ENST00000946233.1		c.792C>G	p.Leu264Leu	synonymous	Exon 5 of 5	ENSP00000616292.1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18119

AN:

151974

Hom.:

1395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.156

AC:

38816

AN:

249536

AF XY:

0.153

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.131

AC:

191946

AN:

1461840

Hom.:

13892

Cov.:

AF XY:

0.132

AC XY:

96163

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0355

AC:

1188

AN:

33480

American (AMR)

AF:

0.249

AC:

11146

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

5603

AN:

26136

East Asian (EAS)

AF:

0.166

AC:

6602

AN:

39700

South Asian (SAS)

AF:

0.155

AC:

13399

AN:

86258

European-Finnish (FIN)

AF:

0.175

AC:

9361

AN:

53372

Middle Eastern (MID)

AF:

0.187

AC:

1078

AN:

5768

European-Non Finnish (NFE)

AF:

0.122

AC:

135296

AN:

1112008

Other (OTH)

AF:

0.137

AC:

8273

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12177

24354

36530

48707

60884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4998

9996

14994

19992

24990

<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:

0.119

AC:

18118

AN:

152092

Hom.:

1394

Cov.:

AF XY:

0.126

AC XY:

9337

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0396

AC:

1643

AN:

41536

American (AMR)

AF:

0.207

AC:

3164

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

698

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

923

AN:

5154

South Asian (SAS)

AF:

0.149

AC:

718

AN:

4814

European-Finnish (FIN)

AF:

0.191

AC:

2021

AN:

10574

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8466

AN:

67970

Other (OTH)

AF:

0.132

AC:

276

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

776

1552

2328

3104

3880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.130

Hom.:

448

Bravo

AF:

0.119

Asia WGS

AF:

0.118

AC:

410

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.129

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.8

(source)

DANN

Benign

0.84

PhyloP100

0.024

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over