rs1681957

Variant names:

• chr6-63513240-T-C
• rs1681957
• ENST00000701584.1:n.133+52858A>G

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.133+52858A>G 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 152,018 control chromosomes in the GnomAD database, including 23,631 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 (23631 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-964+52262A>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+52858A>G		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825503.1	n.130+52858A>G		intron_variant	Intron 1 of 3
ENSG00000289911	ENST00000825504.1	n.145+52262A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81286 AN: 151898 Hom.: 23572 Cov.: 32

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.536 AC: 81414 AN: 152018 Hom.: 23631 Cov.: 32 AF XY: 0.532 AC XY: 39493 AN XY: 74298

African (AFR) AF: 0.771 AC: 31972 AN: 41452

American (AMR) AF: 0.534 AC: 8151 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3472

East Asian (EAS) AF: 0.449 AC: 2315 AN: 5158

South Asian (SAS) AF: 0.492 AC: 2371 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4038 AN: 10560

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29644 AN: 67974

Other (OTH) AF: 0.495 AC: 1046 AN: 2114

Alfa AF: 0.500 Hom.: 3394

Bravo AF: 0.557

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.32
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1681957; hg19: chr6-64223145; COSMIC: COSV63777655;