Variant 17-6426833-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014336.5(AIPL1):c.642+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,612,774 control chromosomes in the GnomAD database, including 107,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10052 hom., cov: 33)

Exomes 𝑓: 0.36 ( 97251 hom. )

Consequence

AIPL1
NM_014336.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.63

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 (BayesDel_noAF=-0.9).

BP6

Variant 17-6426833-C-T is Benign according to our data. Variant chr17-6426833-C-T is described in ClinVar as [Benign]. Clinvar id is 1239041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6426833-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIPL1	NM_014336.5 linkuse as main transcript	c.642+48G>A		intron_variant		ENST00000381129.8	NP_055151.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000381129.8 linkuse as main transcript	c.642+48G>A		intron_variant		1	NM_014336.5	ENSP00000370521	P1	Q9NZN9-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54959

AN:

151928

Hom.:

10038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.363

AC:

90736

AN:

249752

Hom.:

16954

AF XY:

0.361

AC XY:

48788

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.462

Gnomad SAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.416

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.363

AC:

530076

AN:

1460730

Hom.:

97251

Cov.:

AF XY:

0.362

AC XY:

262921

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.477

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.362

AC:

55005

AN:

152044

Hom.:

10052

Cov.:

AF XY:

0.363

AC XY:

26966

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.398

Gnomad4 EAS

AF:

0.468

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.421

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.303

Hom.:

1258

Bravo

AF:

0.356

Asia WGS

AF:

0.391

AC:

1356

AN:

3478

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	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.27

DANN

Benign

0.67

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