17-6398242-A-G

Position:

• chr17-6398242-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570584.5(AIPL1):​c.250-4392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,168 control chromosomes in the GnomAD database, including 54,876 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54876 hom., cov: 32)
• Consequence: AIPL1 ENST00000570584.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000570584.5	c.250-4392T>C		intron_variant		3		ENSP00000467360.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128337 AN: 152050 Hom.: 54835 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.844 AC: 128433 AN: 152168 Hom.: 54876 Cov.: 32 AF XY: 0.838 AC XY: 62352 AN XY: 74398

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.812

Alfa AF: 0.829 Hom.: 107583

Bravo AF: 0.841

Asia WGS AF: 0.675 AC: 2349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.5
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1606610; hg19: chr17-6301562;