6-79485476-C-T

Variant names:

• chr6-79485476-C-T
• rs41269343
• NM_001122769.3:c.*1528G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.51
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• LCA5-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000231533 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 358071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122769.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCA5	NM_001122769.3	MANE Select	c.*1528G>A		3_prime_UTR	Exon 8 of 8	NP_001116241.1	A0A384MDJ7
	LCA5	NM_181714.4		c.*1528G>A		3_prime_UTR	Exon 9 of 9	NP_859065.2	A0A384MDJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCA5	ENST00000369846.9	TSL:1 MANE Select	c.*1528G>A		3_prime_UTR	Exon 8 of 8	ENSP00000358861.4	Q86VQ0
	LCA5	ENST00000392959.5	TSL:1	c.*1528G>A		3_prime_UTR	Exon 9 of 9	ENSP00000376686.1	Q86VQ0
	LCA5	ENST00000859359.1		c.*1528G>A		3_prime_UTR	Exon 8 of 8	ENSP00000529418.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.136 AC: 54 AN: 396

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.117 AC: 4870 AN: 41458

American (AMR) AF: 0.0843 AC: 1286 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0684 AC: 237 AN: 3466

East Asian (EAS) AF: 0.00948 AC: 49 AN: 5170

South Asian (SAS) AF: 0.0322 AC: 155 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1303 AN: 10516

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8982 AN: 67942

Other (OTH) AF: 0.102 AC: 214 AN: 2108

Alfa AF: 0.0613 Hom.: 74

Bravo AF: 0.110

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0090
DANN	Benign	0.39
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41269343; hg19: chr6-80195193;