rs11869118

Variant names:

• chr17-6424171-C-T
• rs11869118
• NM_014336.5:c.*1289G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-6424171-C-T
• chr17-6424171-C-A

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.*1289G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 152,354 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (483 hom., cov: 33)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: AIPL1 NM_014336.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.637
• Publications: 4 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=-0.91).
• BP6: Variant 17-6424171-C-T is Benign according to our data. Variant chr17-6424171-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 324579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0827 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.*1289G>A		3_prime_UTR	Exon 6 of 6	NP_055151.3
	AIPL1	NM_001285399.3		c.*1289G>A		3_prime_UTR	Exon 6 of 6	NP_001272328.1	Q7Z3H1
	AIPL1	NM_001285400.3		c.*1289G>A		3_prime_UTR	Exon 6 of 6	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.*1289G>A		3_prime_UTR	Exon 6 of 6	ENSP00000370521.3	Q9NZN9-1
	AIPL1	ENST00000250087.9	TSL:1	c.*1289G>A		3_prime_UTR	Exon 5 of 5	ENSP00000250087.5	Q9NZN9-3
	AIPL1	ENST00000381128.2	TSL:1	n.*2316G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000370520.2	J3KPI5

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11581 AN: 152146 Hom.: 482 Cov.: 33

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0611

GnomAD4 exome AF: 0.111 AC: 10 AN: 90 Hom.: 0 Cov.: 0 AF XY: 0.109 AC XY: 7 AN XY: 64

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.111 AC: 2 AN: 18

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.121 AC: 7 AN: 58

Other (OTH) AF: 0.100 AC: 1 AN: 10

GnomAD4 genome AF: 0.0762 AC: 11596 AN: 152264 Hom.: 483 Cov.: 33 AF XY: 0.0752 AC XY: 5597 AN XY: 74452

African (AFR) AF: 0.0754 AC: 3131 AN: 41538

American (AMR) AF: 0.0501 AC: 767 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 188 AN: 3472

East Asian (EAS) AF: 0.0580 AC: 301 AN: 5188

South Asian (SAS) AF: 0.0764 AC: 369 AN: 4830

European-Finnish (FIN) AF: 0.0809 AC: 858 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0845 AC: 5746 AN: 68008

Other (OTH) AF: 0.0600 AC: 127 AN: 2116

Alfa AF: 0.0210 Hom.: 10

Bravo AF: 0.0741

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 4 (1)
-	-	1	not provided (1)
-	-	1	Retinitis Pigmentosa, Dominant (1)
-	-	1	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11869118; hg19: chr17-6327491;