Variant chr6-79485704-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001122769.3(LCA5):c.*1300G>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 0.0256 in 152,190 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LCA5
NM_001122769.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0420

Variant links:

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]

LCA5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-79485704-C-T is Benign according to our data. Variant chr6-79485704-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 358073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0256 (3900/152190) while in subpopulation SAS AF= 0.0423 (204/4820). AF 95% confidence interval is 0.0376. There are 58 homozygotes in gnomad4. There are 1915 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCA5	NM_001122769.3 linkuse as main transcript	c.*1300G>A		3_prime_UTR_variant	8/8	ENST00000369846.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
LCA5	ENST00000369846.9 linkuse as main transcript	c.*1300G>A	3_prime_UTR_variant	8/8	1	NM_001122769.3	P1
LCA5	ENST00000392959.5 linkuse as main transcript	c.*1300G>A	3_prime_UTR_variant	9/9	1		P1
	ENST00000652956.1 linkuse as main transcript	n.469+4264C>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3903

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00575

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0567

Gnomad EAS

AF:

0.0394

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.0833

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.0411

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.0256

AC:

3900

AN:

152190

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

1915

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00573

Gnomad4 AMR

AF:

0.0257

Gnomad4 ASJ

AF:

0.0567

Gnomad4 EAS

AF:

0.0395

Gnomad4 SAS

AF:

0.0423

Gnomad4 FIN

AF:

0.0224

Gnomad4 NFE

AF:

0.0340

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.0247

Asia WGS

AF:

0.0330

AC:

115

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

1.1

DANN

Benign

0.54

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

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