6-79538609-C-G

Variant names:

• chr6-79538609-C-G
• rs2655693
• XM_047418251.1:c.-192+89G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047418251.1(LCA5):​c.-192+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 XM_047418251.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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]

ENSG00000287811 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCA5	XM_047418251.1	c.-192+89G>C		intron_variant	Intron 1 of 7		XP_047274207.1
SH3BGRL2	XM_047419390.1	c.25-119C>G		intron_variant	Intron 1 of 3		XP_047275346.1
SH3BGRL2	XM_047419391.1	c.-5157-119C>G		intron_variant	Intron 1 of 5		XP_047275347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287811	ENST00000671258.1	n.174-119C>G		intron_variant	Intron 1 of 1
ENSG00000287811	ENST00000691944.1	n.298-119C>G		intron_variant	Intron 1 of 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

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.325

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2655693; hg19: chr6-80248326;