rs2984458

Variant names:

• chr6-63505258-T-C
• rs2984458
• XM_047418866.1:c.-964+60244A>G

Variant summary

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

The XM_047418866.1(LGSN):​c.-964+60244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 150,674 control chromosomes in the GnomAD database, including 23,312 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 0.53 (23312 hom., cov: 27)
• Consequence: LGSN XM_047418866.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-964+60244A>G		intron_variant	Intron 1 of 11		XP_047274822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000701584.1	n.133+60840A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80355 AN: 150556 Hom.: 23255 Cov.: 27

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.534 AC: 80480 AN: 150674 Hom.: 23312 Cov.: 27 AF XY: 0.530 AC XY: 38955 AN XY: 73510

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.493

Alfa AF: 0.452 Hom.: 13872

Bravo AF: 0.557

Asia WGS AF: 0.455 AC: 1581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2984458; hg19: chr6-64215163;