chr6-63483202-C-T

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000701584.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289911	ENST00000701584.1		n.134-39444G>A		intron	N/A
	ENSG00000289911	ENST00000825503.1		n.131-39444G>A		intron	N/A
	ENSG00000289911	ENST00000825504.1		n.146-39444G>A		intron	N/A

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 v4.9

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;