rs2076874

Variant names:

• chr6-63443786-G-A
• rs2076874
• XM_047418866.1:c.-963-28C>T

Variant summary

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

The XM_047418866.1(LGSN):​c.-963-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,880 control chromosomes in the GnomAD database, including 25,976 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 0.58 (25976 hom., cov: 30)
• Consequence: LGSN XM_047418866.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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]

LOC642554 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-963-28C>T		intron_variant	Intron 1 of 11		XP_047274822.1
LOC642554		n.63443786G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000701584.1	n.134-28C>T		intron_variant	Intron 1 of 5
ENSG00000218048	ENST00000402043.2	n.*206G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88332 AN: 151762 Hom.: 25965 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.582 AC: 88386 AN: 151880 Hom.: 25976 Cov.: 30 AF XY: 0.586 AC XY: 43497 AN XY: 74228

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.598

Alfa AF: 0.575 Hom.: 3107

Bravo AF: 0.571

Asia WGS AF: 0.634 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2076874; hg19: chr6-64153691;