rs2758259

Variant names:

• chr6-63483202-C-T
• rs2758259
• ENST00000701584.1:n.134-39444G>A

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.134-39444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,972 control chromosomes in the GnomAD database, including 23,683 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 0.54 (23683 hom., cov: 31)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 4 publications found

Genes affected

ENSG00000289911 (HGNC:):

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]

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 (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-963-39444G>A		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.134-39444G>A		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825503.1	n.131-39444G>A		intron_variant	Intron 1 of 3
ENSG00000289911	ENST00000825504.1	n.146-39444G>A		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825505.1	n.93-39444G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81386 AN: 151854 Hom.: 23628 Cov.: 31

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.536 AC: 81509 AN: 151972 Hom.: 23683 Cov.: 31 AF XY: 0.533 AC XY: 39544 AN XY: 74260

African (AFR) AF: 0.772 AC: 32027 AN: 41478

American (AMR) AF: 0.536 AC: 8195 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2330 AN: 5172

South Asian (SAS) AF: 0.487 AC: 2345 AN: 4818

European-Finnish (FIN) AF: 0.385 AC: 4049 AN: 10528

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29620 AN: 67916

Other (OTH) AF: 0.496 AC: 1045 AN: 2106

Alfa AF: 0.506 Hom.: 4377

Bravo AF: 0.558

Asia WGS AF: 0.452 AC: 1569 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	2.7
DANN	Benign	0.25
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs2758259; hg19: chr6-64193107;