6-79485887-TCAA-T

Position:

• chr6-79485887-TCAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001122769.3(LCA5):​c.*1114_*1116del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 152,300 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LCA5 NM_001122769.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454

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 -10 ACMG points.

• BP6: Variant 6-79485887-TCAA-T is Benign according to our data. Variant chr6-79485887-TCAA-T is described in ClinVar as [Benign]. Clinvar id is 1879667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00699 (1065/152300) while in subpopulation NFE AF= 0.0101 (686/68008). AF 95% confidence interval is 0.00946. There are 8 homozygotes in gnomad4. There are 550 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCA5	NM_001122769.3	c.*1114_*1116del		3_prime_UTR_variant	8/8	ENST00000369846.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCA5	ENST00000369846.9	c.*1114_*1116del		3_prime_UTR_variant	8/8	1	NM_001122769.3	P1
LCA5	ENST00000392959.5	c.*1114_*1116del		3_prime_UTR_variant	9/9	1		P1
	ENST00000652956.1	n.469+4449_469+4451del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 1065 AN: 152182 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00699 AC: 1065 AN: 152300 Hom.: 8 Cov.: 32 AF XY: 0.00739 AC XY: 550 AN XY: 74474

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.0109 Hom.: 1

Bravo AF: 0.00506

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

LCA5: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs531553621; hg19: chr6-80195604;