rs1630182

Variant names:

• chr6-63498307-G-A
• rs1630182
• ENST00000701584.1:n.134-54549C>T

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.134-54549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,794 control chromosomes in the GnomAD database, including 23,566 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 (23566 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-963-54549C>T		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.134-54549C>T		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825503.1	n.131-54549C>T		intron_variant	Intron 1 of 3
ENSG00000289911	ENST00000825504.1	n.146-54549C>T		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81053 AN: 151676 Hom.: 23508 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.535 AC: 81180 AN: 151794 Hom.: 23566 Cov.: 32 AF XY: 0.531 AC XY: 39384 AN XY: 74176

African (AFR) AF: 0.769 AC: 31758 AN: 41288

American (AMR) AF: 0.533 AC: 8139 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2328 AN: 5172

South Asian (SAS) AF: 0.494 AC: 2376 AN: 4810

European-Finnish (FIN) AF: 0.383 AC: 4034 AN: 10544

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29633 AN: 67942

Other (OTH) AF: 0.492 AC: 1034 AN: 2102

Alfa AF: 0.483 Hom.: 6124

Bravo AF: 0.556

Asia WGS AF: 0.455 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.58
PhyloP100		0.91

Splicing

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

Other links and lift over

dbSNP: rs1630182; hg19: chr6-64208212;