chr17-6434084-G-A

Position:

chr17-6434084-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_014336.5(AIPL1):c.111C>T(p.Phe37Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,613,834 control chromosomes in the GnomAD database, including 748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 58 hom., cov: 30)

Exomes 𝑓: 0.027 ( 690 hom. )

Consequence

AIPL1
NM_014336.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:2

Conservation

PhyloP100: 2.40

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 17-6434084-G-A is Benign according to our data. Variant chr17-6434084-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 99789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6434084-G-A is described in Lovd as [Benign]. Variant chr17-6434084-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2905/152166) while in subpopulation NFE AF= 0.0285 (1940/67996). AF 95% confidence interval is 0.0275. There are 58 homozygotes in gnomad4. There are 1469 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIPL1	NM_014336.5 linkuse as main transcript	c.111C>T	p.Phe37Phe	synonymous_variant	2/6	ENST00000381129.8	NP_055151.3	Q9NZN9-1F1T0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000381129.8 linkuse as main transcript	c.111C>T	p.Phe37Phe	synonymous_variant	2/6	1	NM_014336.5	ENSP00000370521.3		Q9NZN9-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2905

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00544

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0518

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.0206

AC:

5159

AN:

250950

Hom.:

104

AF XY:

0.0205

AC XY:

2785

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00542

Gnomad AMR exome

AF:

0.00440

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000851

Gnomad FIN exome

AF:

0.0496

Gnomad NFE exome

AF:

0.0322

Gnomad OTH exome

AF:

0.0229

GnomAD4 exome

AF:

0.0269

AC:

39323

AN:

1461668

Hom.:

690

Cov.:

AF XY:

0.0261

AC XY:

19009

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.0495

Gnomad4 NFE exome

AF:

0.0315

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0191

AC:

2905

AN:

152166

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1469

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00542

Gnomad4 AMR

AF:

0.00700

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0518

Gnomad4 NFE

AF:

0.0285

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0232

EpiControl

AF:

0.0237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
not provided, no classification provided	literature only	Retina International	-	- -

Leber congenital amaurosis 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Retinitis Pigmentosa, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis Pigmentosa, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.7

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

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