rs865416

Positions:

• chr6-63404288-A-C

Variant summary

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

The XM_017010930.3(LGSN):​c.-651+218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,116 control chromosomes in the GnomAD database, including 1,988 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 0.11 (1988 hom., cov: 32)
• Consequence: LGSN XM_017010930.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

LGSN (HGNC:21016): (lengsin, lens protein with glutamine synthetase domain) This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ENSG00000289911 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGSN	XM_017010930.3	c.-651+218T>G		intron_variant			XP_016866419.1
LGSN	XM_047418866.1	c.-789+218T>G		intron_variant			XP_047274822.1
LGSN	XM_011535892.4	c.-666+218T>G		intron_variant			XP_011534194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000701584.1	n.308+218T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17421 AN: 151998 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.115 AC: 17479 AN: 152116 Hom.: 1988 Cov.: 32 AF XY: 0.113 AC XY: 8382 AN XY: 74394

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.0615

Gnomad4 SAS AF: 0.0812

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.0878 Hom.: 214

Bravo AF: 0.128

Asia WGS AF: 0.0840 AC: 293 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	0.44
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs865416; hg19: chr6-64114193;