17-6424231-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014336.5(AIPL1):c.*1229C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,172 control chromosomes in the GnomAD database, including 6,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6258 hom., cov: 33)

Exomes 𝑓: 0.32 ( 5 hom. )

Consequence

AIPL1
NM_014336.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.539

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 17-6424231-G-A is Benign according to our data. Variant chr17-6424231-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 324581.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 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.*1229C>T		3_prime_UTR_variant	6/6	ENST00000381129.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIPL1	ENST00000381129.8 linkuse as main transcript	c.*1229C>T	3_prime_UTR_variant	6/6	1	NM_014336.5	P1	Q9NZN9-1
AIPL1	ENST00000250087.9 linkuse as main transcript	c.*1229C>T	3_prime_UTR_variant	5/5	1			Q9NZN9-3
AIPL1	ENST00000381128.2 linkuse as main transcript	c.*2256C>T	3_prime_UTR_variant, NMD_transcript_variant	6/6	1
AIPL1	ENST00000570584.5 linkuse as main transcript	c.251+9688C>T	intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43169

AN:

151982

Hom.:

6250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.319

AC:

AN:

Hom.:

Cov.:

AF XY:

0.357

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.284

AC:

43212

AN:

152100

Hom.:

6258

Cov.:

AF XY:

0.285

AC XY:

21211

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.240

Gnomad4 AMR

AF:

0.314

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.297

Hom.:

8858

Bravo

AF:

0.283

Asia WGS

AF:

0.309

AC:

1077

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leber congenital amaurosis 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Retinitis Pigmentosa, Dominant

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 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

Cadd

Benign

3.4

Dann

Benign

0.35

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