17-6428483-T-C

Position:

chr17-6428483-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014336.5(AIPL1):c.300A>G(p.Leu100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,613,462 control chromosomes in the GnomAD database, including 335,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28856 hom., cov: 34)

Exomes 𝑓: 0.65 ( 306962 hom. )

Consequence

AIPL1
NM_014336.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.306

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 17-6428483-T-C is Benign according to our data. Variant chr17-6428483-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 166655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6428483-T-C is described in Lovd as [Benign]. Variant chr17-6428483-T-C is described in Lovd as [Likely_pathogenic]. Variant chr17-6428483-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.306 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIPL1	NM_014336.5 linkuse as main transcript	c.300A>G	p.Leu100=	synonymous_variant	3/6	ENST00000381129.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIPL1	ENST00000381129.8 linkuse as main transcript	c.300A>G	p.Leu100=	synonymous_variant	3/6	1	NM_014336.5	P1	Q9NZN9-1

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92833

AN:

152074

Hom.:

28841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.766

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.656

GnomAD3 exomes

AF:

0.643

AC:

161264

AN:

250792

Hom.:

52550

AF XY:

0.644

AC XY:

87368

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.708

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.548

Gnomad SAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.661

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.646

AC:

944099

AN:

1461270

Hom.:

306962

Cov.:

AF XY:

0.646

AC XY:

469961

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.702

Gnomad4 ASJ exome

AF:

0.770

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.618

Gnomad4 FIN exome

AF:

0.616

Gnomad4 NFE exome

AF:

0.652

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.610

AC:

92904

AN:

152192

Hom.:

28856

Cov.:

AF XY:

0.607

AC XY:

45177

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.664

Gnomad4 ASJ

AF:

0.766

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.605

Gnomad4 FIN

AF:

0.618

Gnomad4 NFE

AF:

0.664

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.661

Hom.:

67111

Bravo

AF:

0.611

Asia WGS

AF:

0.550

AC:

1913

AN:

3478

EpiCase

AF:

0.678

EpiControl

AF:

0.683

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 20, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Leber congenital amaurosis 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Retinitis Pigmentosa, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.2

DANN

Benign

0.66

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