rs62635774

Variant names:

• chr17-6433961-G-A
• rs62635774
• NM_014336.5:c.234C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6433961-G-A
• chr17-6433961-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_014336.5(AIPL1):​c.234C>T​(p.Ser78Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,613,838 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00019 (2 hom.)
• Consequence: AIPL1 NM_014336.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2 O:1
• Conservation: PhyloP100: 2.45

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-6433961-G-A is Benign according to our data. Variant chr17-6433961-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 99791.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=2, not_provided=1}. Variant chr17-6433961-G-A is described in Lovd as [Benign]. Variant chr17-6433961-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.001 (152/152036) while in subpopulation AFR AF= 0.00348 (144/41358). AF 95% confidence interval is 0.00302. There are 1 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIPL1	NM_014336.5	c.234C>T	p.Ser78Ser	synonymous_variant	Exon 2 of 6	ENST00000381129.8	NP_055151.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000381129.8	c.234C>T	p.Ser78Ser	synonymous_variant	Exon 2 of 6	1	NM_014336.5	ENSP00000370521.3

Frequencies

GnomAD3 genomes AF: 0.000968 AC: 147 AN: 151918 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000287 AC: 72 AN: 251118 Hom.: 0 AF XY: 0.000273 AC XY: 37 AN XY: 135732

Gnomad AFR exome AF: 0.00345

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000189 AC: 277 AN: 1461802 Hom.: 2 Cov.: 33 AF XY: 0.000194 AC XY: 141 AN XY: 727190

Gnomad4 AFR exome AF: 0.00457

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.00100 AC: 152 AN: 152036 Hom.: 1 Cov.: 30 AF XY: 0.00109 AC XY: 81 AN XY: 74336

Gnomad4 AFR AF: 0.00348

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000494 Hom.: 0

Bravo AF: 0.00101

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:2 Other:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Leber congenital amaurosis 4 Uncertain:1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa Uncertain:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not specified Benign:1

Jun 24, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Other:1

-

Retina International

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.8
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs62635774; hg19: chr17-6337281;