Genetic Variant NM_014336.5:c.-106C>A (chr17-6435210-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014336.5(AIPL1):c.-106C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,492,424 control chromosomes in the GnomAD database, including 11,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1047 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10284 hom. )

Consequence

AIPL1
NM_014336.5 upstream_gene

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.559

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-6435210-G-T is Benign according to our data. Variant chr17-6435210-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 369221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6435210-G-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIPL1	NM_014336.5 link	c.-106C>A		upstream_gene_variant		ENST00000381129.8	NP_055151.3	Q9NZN9-1F1T0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000381129.8 link	c.-106C>A		upstream_gene_variant		1	NM_014336.5	ENSP00000370521.3		Q9NZN9-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15868

AN:

152016

Hom.:

1047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.0892

Gnomad FIN

AF:

0.0951

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.112

AC:

149849

AN:

1340288

Hom.:

10284

Cov.:

AF XY:

0.113

AC XY:

74960

AN XY:

666248

show subpopulations

Gnomad4 AFR exome

AF:

0.0538

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.0928

Gnomad4 FIN exome

AF:

0.0853

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.104

AC:

15863

AN:

152136

Hom.:

1047

Cov.:

AF XY:

0.106

AC XY:

7846

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0544

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.291

Gnomad4 SAS

AF:

0.0899

Gnomad4 FIN

AF:

0.0951

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.113

Hom.:

1467

Bravo

AF:

0.113

Asia WGS

AF:

0.168

AC:

581

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Leber congenital amaurosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis Pigmentosa, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.9

DANN

Benign

0.66

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over