Variant chr2-63056043-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

OTX1 (HGNC:):

OTX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTX1	NM_014562.4 linkuse as main transcript	c.792C>G	p.Leu264Leu	synonymous_variant	5/5	ENST00000282549.7	NP_055377.1	P32242
OTX1	NM_001199770.2 linkuse as main transcript	c.792C>G	p.Leu264Leu	synonymous_variant	5/5		NP_001186699.1	P32242
OTX1	NR_130153.2 linkuse as main transcript	n.1155C>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OTX1	ENST00000282549.7 linkuse as main transcript	c.792C>G	p.Leu264Leu	synonymous_variant	5/5	1	NM_014562.4	ENSP00000282549.2	P32242
OTX1	ENST00000366671.7 linkuse as main transcript	c.792C>G	p.Leu264Leu	synonymous_variant	5/5	3		ENSP00000355631.3	P32242
OTX1	ENST00000405984.8 linkuse as main transcript	n.*601C>G		non_coding_transcript_exon_variant	5/5	2		ENSP00000385782.4	B5MC54
OTX1	ENST00000405984.8 linkuse as main transcript	n.*601C>G		3_prime_UTR_variant	5/5	2		ENSP00000385782.4	B5MC54

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

GnomAD3 exomes

AF:

0.156

AC:

38816

AN:

249536

Hom.:

3545

AF XY:

0.153

AC XY:

20605

AN XY:

135030

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 SAS exome

AF:

0.152

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

Gnomad4 AFR exome

AF:

0.0355

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.119

AC:

18118

AN:

152092

Hom.:

1394

Cov.:

AF XY:

0.126

AC XY:

9337

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0396

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.132

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.8

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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