rs2292545

chr17-6426789-G-Achr17-6426789-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014336.5(AIPL1):c.643-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,612,572 control chromosomes in the GnomAD database, including 57,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4643 hom., cov: 33)
  • Exomes 𝑓: 0.26 (52689 hom.)
• Consequence: AIPL1 NM_014336.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0770

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-6426789-G-A is Benign according to our data. Variant chr17-6426789-G-A is described in ClinVar as [Benign]. Clinvar id is 1257409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIPL1	NM_014336.5	c.643-33C>T		intron_variant		ENST00000381129.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIPL1	ENST00000381129.8	c.643-33C>T		intron_variant		1	NM_014336.5	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34814 AN: 151976 Hom.: 4645 Cov.: 33

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.262 AC: 65459 AN: 250198 Hom.: 9422 AF XY: 0.258 AC XY: 34915 AN XY: 135342

Gnomad AFR exome AF: 0.0924

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.133

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.263 AC: 383719 AN: 1460480 Hom.: 52689 Cov.: 45 AF XY: 0.261 AC XY: 189360 AN XY: 726594

Gnomad4 AFR exome AF: 0.0917

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.229 AC: 34799 AN: 152092 Hom.: 4643 Cov.: 33 AF XY: 0.231 AC XY: 17199 AN XY: 74354

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.277

Alfa AF: 0.237 Hom.: 1481

Bravo AF: 0.219

Asia WGS AF: 0.212 AC: 736 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.79
Cadd	Benign	2.0
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2292545; hg19: chr17-6330109; COSMIC: COSV51508307; COSMIC: COSV51508307;