6-79538609-C-G

Variant names:

• chr6-79538609-C-G
• rs2655693
• ENST00000951447.1:c.-298+89G>C

Variant summary

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

The ENST00000951447.1(LCA5):​c.-298+89G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,058 control chromosomes in the GnomAD database, including 8,711 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 (8711 hom., cov: 33)
• Consequence: LCA5 ENST00000951447.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 4 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]

SH3BGRL2 (HGNC:15567): (SH3 domain binding glutamate rich protein like 2) Predicted to enable SH3 domain binding activity. Located in nuclear membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000951447.1. 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
	SH3BGRL2	NR_171675.1		n.253-119C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCA5	ENST00000951447.1		c.-298+89G>C		intron	N/A	ENSP00000621506.1
	SH3BGRL2	ENST00000718102.1		c.25-119C>G		intron	N/A	ENSP00000520671.1
	SH3BGRL2	ENST00000718104.1		c.-36-119C>G		intron	N/A	ENSP00000520672.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48167 AN: 151940 Hom.: 8696 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.317 AC: 48224 AN: 152058 Hom.: 8711 Cov.: 33 AF XY: 0.326 AC XY: 24207 AN XY: 74348

African (AFR) AF: 0.280 AC: 11626 AN: 41466

American (AMR) AF: 0.458 AC: 6994 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.808 AC: 4184 AN: 5178

South Asian (SAS) AF: 0.436 AC: 2103 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3220 AN: 10552

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 18097 AN: 67974

Other (OTH) AF: 0.325 AC: 687 AN: 2112

Alfa AF: 0.164 Hom.: 309

Bravo AF: 0.334

Asia WGS AF: 0.580 AC: 2017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		-0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2655693; hg19: chr6-80248326;