ENST00000575265.5:c.802G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000575265.5(AIPL1):c.802G>A(p.Gly268Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,611,942 control chromosomes in the GnomAD database, including 1,612 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G268G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.053 ( 515 hom., cov: 33)

Exomes 𝑓: 0.021 ( 1097 hom. )

Consequence

AIPL1
ENST00000575265.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.145

Variant links:

Genes affected

AIPL1 (HGNC:359): (aryl hydrocarbon receptor interacting protein like 1) Leber congenital amaurosis (LCA) is the most severe inherited retinopathy with the earliest age of onset and accounts for at least 5% of all inherited retinal diseases. Affected individuals are diagnosed at birth or in the first few months of life with nystagmus, severely impaired vision or blindness and an abnormal or flat electroretinogram. The photoreceptor/pineal-expressed gene, AIPL1, encoding aryl-hydrocarbon interacting protein-like 1, is located within the LCA4 candidate region. The encoded protein contains three tetratricopeptide motifs, consistent with chaperone or nuclear transport activity. Mutations in this gene may cause approximately 20% of recessive LCA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

AIPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021551847).

BP6

Variant 17-6426597-C-T is Benign according to our data. Variant chr17-6426597-C-T is described in ClinVar as [Benign]. Clinvar id is 99807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6426597-C-T is described in Lovd as [Benign]. Variant chr17-6426597-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIPL1	NM_014336.5 link	c.784+18G>A		intron_variant	Intron 5 of 5	ENST00000381129.8	NP_055151.3	Q9NZN9-1F1T0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000381129.8 link	c.784+18G>A		intron_variant	Intron 5 of 5	1	NM_014336.5	ENSP00000370521.3		Q9NZN9-1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8105

AN:

152176

Hom.:

510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.0497

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0336

AC:

8321

AN:

247650

Hom.:

411

AF XY:

0.0350

AC XY:

4698

AN XY:

134166

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.00912

Gnomad ASJ exome

AF:

0.00490

Gnomad EAS exome

AF:

0.0488

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.0246

GnomAD4 exome

AF:

0.0207

AC:

30256

AN:

1459648

Hom.:

1097

Cov.:

AF XY:

0.0226

AC XY:

16420

AN XY:

726124

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.00437

Gnomad4 EAS exome

AF:

0.0473

Gnomad4 SAS exome

AF:

0.0990

Gnomad4 FIN exome

AF:

0.0124

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0534

AC:

8135

AN:

152294

Hom.:

515

Cov.:

AF XY:

0.0543

AC XY:

4044

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0260

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.0496

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0280

Hom.:

Bravo

AF:

0.0553

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.143

AC:

630

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.0377

AC:

4581

Asia WGS

AF:

0.0980

AC:

338

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Retina International

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jul 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Leber congenital amaurosis 4

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.24

CADD

Benign

4.3

DANN

Benign

0.46

DEOGEN2

Benign

0.0057

.;T

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0022

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0010

B;.

Vest4

0.065

GERP RS

0.61

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