rs1779758

Positions:

• chr6-63370162-A-G

Variant summary

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

The XM_017010930.3(LGSN):​c.-288+9134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,208 control chromosomes in the GnomAD database, including 2,879 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 0.13 (2879 hom., cov: 32)
• Consequence: LGSN XM_017010930.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGSN	XM_017010930.3	c.-288+9134T>C		intron_variant			XP_016866419.1
LGSN	XM_047418866.1	c.-288+9134T>C		intron_variant			XP_047274822.1
LGSN	XM_011535892.4	c.-303+9134T>C		intron_variant			XP_011534194.1
		n.63370162A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19829 AN: 152090 Hom.: 2862 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.131 AC: 19888 AN: 152208 Hom.: 2879 Cov.: 32 AF XY: 0.128 AC XY: 9506 AN XY: 74432

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0279

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0727 Hom.: 247

Bravo AF: 0.144

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1779758; hg19: chr6-64080067;