6-79485476-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001122769.3(LCA5):c.*1528G>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 0.114 in 152,348 control chromosomes in the GnomAD database, including 1,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1106 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: LCA5 NM_001122769.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.51

Genes affected

LCA5 (HGNC:31923): (lebercilin LCA5) This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described. [provided by RefSeq, Oct 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-79485476-C-T is Benign according to our data. Variant chr6-79485476-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 358071.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCA5	NM_001122769.3	c.*1528G>A		3_prime_UTR_variant	8/8	ENST00000369846.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCA5	ENST00000369846.9	c.*1528G>A		3_prime_UTR_variant	8/8	1	NM_001122769.3	P1
LCA5	ENST00000392959.5	c.*1528G>A		3_prime_UTR_variant	9/9	1		P1
	ENST00000652956.1	n.469+4036C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17275 AN: 151828 Hom.: 1106 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0684

Gnomad EAS AF: 0.00946

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.135 AC: 54 AN: 400 Hom.: 1 Cov.: 0 AF XY: 0.143 AC XY: 35 AN XY: 244

Gnomad4 FIN exome AF: 0.136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.114 AC: 17285 AN: 151948 Hom.: 1106 Cov.: 32 AF XY: 0.110 AC XY: 8175 AN XY: 74258

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0843

Gnomad4 ASJ AF: 0.0684

Gnomad4 EAS AF: 0.00948

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0583 Hom.: 67

Bravo AF: 0.110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber congenital amaurosis 5 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0090
Dann	Benign	0.39

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: rs41269343; hg19: chr6-80195193;