rs907937

Variant names:

• chr17-6424258-G-A
• rs907937
• NM_014336.5:c.*1202C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6424258-G-A
• chr17-6424258-G-C
• chr17-6424258-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.*1202C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,238 control chromosomes in the GnomAD database, including 1,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (1429 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AIPL1 NM_014336.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.365
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BP6: Variant 17-6424258-G-A is Benign according to our data. Variant chr17-6424258-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 324582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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.*1202C>T		3_prime_UTR	Exon 6 of 6	NP_055151.3
	AIPL1	NM_001285399.3		c.*1202C>T		3_prime_UTR	Exon 6 of 6	NP_001272328.1	Q7Z3H1
	AIPL1	NM_001285400.3		c.*1202C>T		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.*1202C>T		3_prime_UTR	Exon 6 of 6	ENSP00000370521.3	Q9NZN9-1
	AIPL1	ENST00000250087.9	TSL:1	c.*1202C>T		3_prime_UTR	Exon 5 of 5	ENSP00000250087.5	Q9NZN9-3
	AIPL1	ENST00000381128.2	TSL:1	n.*2229C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000370520.2	J3KPI5

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15066 AN: 152120 Hom.: 1419 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0909

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0993 AC: 15116 AN: 152238 Hom.: 1429 Cov.: 33 AF XY: 0.0978 AC XY: 7284 AN XY: 74450

African (AFR) AF: 0.244 AC: 10131 AN: 41506

American (AMR) AF: 0.122 AC: 1871 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.0369 AC: 191 AN: 5170

South Asian (SAS) AF: 0.0592 AC: 286 AN: 4830

European-Finnish (FIN) AF: 0.0223 AC: 237 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2052 AN: 68022

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.0569 Hom.: 622

Bravo AF: 0.115

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/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 (1)
-	-	1	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		0.36
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: rs907937; hg19: chr17-6327578;