NM_001122769.3:c.-192+4370T>G

Variant names:

• chr6-79532795-A-C
• rs9352745
• NM_001122769.3:c.-192+4370T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122769.3(LCA5):​c.-192+4370T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,906 control chromosomes in the GnomAD database, including 9,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9030 hom., cov: 32)
• Consequence: LCA5 NM_001122769.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCA5	NM_001122769.3	c.-192+4370T>G		intron_variant	Intron 1 of 7	ENST00000369846.9	NP_001116241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCA5	ENST00000369846.9	c.-192+4370T>G		intron_variant	Intron 1 of 7	1	NM_001122769.3	ENSP00000358861.4
LCA5	ENST00000392959.5	c.-298+4321T>G		intron_variant	Intron 1 of 8	1		ENSP00000376686.1
LCA5	ENST00000467898.3	c.-192+4448T>G		intron_variant	Intron 1 of 6	5		ENSP00000474463.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49260 AN: 151786 Hom.: 9005 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.324

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.325 AC: 49325 AN: 151906 Hom.: 9030 Cov.: 32 AF XY: 0.332 AC XY: 24645 AN XY: 74248

African (AFR) AF: 0.309 AC: 12802 AN: 41444

American (AMR) AF: 0.456 AC: 6961 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3460

East Asian (EAS) AF: 0.807 AC: 4171 AN: 5166

South Asian (SAS) AF: 0.439 AC: 2113 AN: 4812

European-Finnish (FIN) AF: 0.304 AC: 3207 AN: 10542

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18082 AN: 67904

Other (OTH) AF: 0.327 AC: 691 AN: 2112

Alfa AF: 0.292 Hom.: 21828

Bravo AF: 0.342

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.46
PhyloP100		-1.3
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: rs9352745; hg19: chr6-80242512;