chr17-6426597-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 10/11 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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

AIPL1-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leber congenital amaurosis 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

AIPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 99807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.0336

AC:

8321

AN:

247650

AF XY:

0.0350

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 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

African (AFR)

AF:

0.153

AC:

5119

AN:

33458

American (AMR)

AF:

0.0104

AC:

465

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00437

AC:

114

AN:

26104

East Asian (EAS)

AF:

0.0473

AC:

1874

AN:

39658

South Asian (SAS)

AF:

0.0990

AC:

8521

AN:

86084

European-Finnish (FIN)

AF:

0.0124

AC:

645

AN:

52084

Middle Eastern (MID)

AF:

0.0313

AC:

179

AN:

5712

European-Non Finnish (NFE)

AF:

0.0105

AC:

11713

AN:

1111572

Other (OTH)

AF:

0.0269

AC:

1626

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1837

3675

5512

7350

9187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.0534

AC:

8135

AN:

152294

Hom.:

515

Cov.:

AF XY:

0.0543

AC XY:

4044

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.142

AC:

5883

AN:

41554

American (AMR)

AF:

0.0260

AC:

398

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3468

East Asian (EAS)

AF:

0.0496

AC:

257

AN:

5178

South Asian (SAS)

AF:

0.113

AC:

545

AN:

4824

European-Finnish (FIN)

AF:

0.0133

AC:

141

AN:

10626

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

793

AN:

68018

Other (OTH)

AF:

0.0378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

365

730

1095

1460

1825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0280

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

Jul 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

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

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.24

CADD

Benign

4.3

(source)

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

PhyloP100

-0.14

Sift4G

Benign

0.22

T;T

Polyphen

0.0010

B;.

Vest4

0.065

GERP RS

0.61

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over