rs1779758

Variant names:

• chr6-63370162-A-G
• rs1779758
• ENST00000825503.1:n.306-19321T>C

Variant summary

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

The ENST00000825503.1(ENSG00000289911):​n.306-19321T>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: ENSG00000289911 ENST00000825503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• 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=-0.91).
• 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 rank	MANE	Protein	UniProt
LGSN	XM_017010930.3	c.-288+9134T>C		intron_variant	Intron 4 of 9		XP_016866419.1
LGSN	XM_047418866.1	c.-288+9134T>C		intron_variant	Intron 6 of 11		XP_047274822.1
LGSN	XM_011535892.4	c.-303+9134T>C		intron_variant	Intron 4 of 9		XP_011534194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000825503.1	n.306-19321T>C		intron_variant	Intron 3 of 3
ENSG00000289911	ENST00000825504.1	n.683+9134T>C		intron_variant	Intron 5 of 5
ENSG00000289911	ENST00000825506.1	n.1095+9134T>C		intron_variant	Intron 4 of 4

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

African (AFR) AF: 0.358 AC: 14830 AN: 41466

American (AMR) AF: 0.0724 AC: 1107 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 97 AN: 3472

East Asian (EAS) AF: 0.158 AC: 820 AN: 5184

South Asian (SAS) AF: 0.0870 AC: 420 AN: 4828

European-Finnish (FIN) AF: 0.0214 AC: 227 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2044 AN: 68024

Other (OTH) AF: 0.108 AC: 228 AN: 2114

Alfa AF: 0.0847 Hom.: 539

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
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs1779758; hg19: chr6-64080067;