rs2292545

Variant names:

• chr17-6426789-G-A
• rs2292545
• NM_014336.5:c.643-33C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6426789-G-A
• chr17-6426789-G-C
• chr17-6426789-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0770
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• AIPL1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1257409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014336.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIPL1	NM_014336.5	MANE Select	c.643-33C>T		intron	N/A	NP_055151.3
	AIPL1	NM_001285399.3		c.607-33C>T		intron	N/A	NP_001272328.1	Q7Z3H1
	AIPL1	NM_001285400.3		c.577-33C>T		intron	N/A	NP_001272329.1	Q9NZN9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIPL1	ENST00000381129.8	TSL:1 MANE Select	c.643-33C>T		intron	N/A	ENSP00000370521.3	Q9NZN9-1
	AIPL1	ENST00000574506.5	TSL:1	c.607-33C>T		intron	N/A	ENSP00000458456.1	Q7Z3H1
	AIPL1	ENST00000570466.5	TSL:1	c.577-33C>T		intron	N/A	ENSP00000461287.1	Q9NZN9-4

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

GnomAD2 exomes AF: 0.262 AC: 65459 AN: 250198 AF XY: 0.258

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 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

African (AFR) AF: 0.0917 AC: 3068 AN: 33470

American (AMR) AF: 0.278 AC: 12430 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8824 AN: 26128

East Asian (EAS) AF: 0.353 AC: 14026 AN: 39698

South Asian (SAS) AF: 0.134 AC: 11567 AN: 86246

European-Finnish (FIN) AF: 0.352 AC: 18429 AN: 52298

Middle Eastern (MID) AF: 0.363 AC: 2094 AN: 5766

European-Non Finnish (NFE) AF: 0.267 AC: 297290 AN: 1111788

Other (OTH) AF: 0.265 AC: 15991 AN: 60376

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

African (AFR) AF: 0.0974 AC: 4042 AN: 41514

American (AMR) AF: 0.248 AC: 3787 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1690 AN: 5158

South Asian (SAS) AF: 0.130 AC: 629 AN: 4822

European-Finnish (FIN) AF: 0.367 AC: 3879 AN: 10566

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18876 AN: 67948

Other (OTH) AF: 0.277 AC: 587 AN: 2116

Alfa AF: 0.256 Hom.: 8791

Bravo AF: 0.219

Asia WGS AF: 0.212 AC: 736 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		0.077
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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