6-63374411-C-T

Variant names:

• chr6-63374411-C-T
• rs1525354
• ENST00000825519.1:n.1748G>A

Variant summary

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

The ENST00000825519.1(ENSG00000289911):​n.1748G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,136 control chromosomes in the GnomAD database, including 2,443 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 0.12 (2443 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000825519.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_017010930.3	c.-288+4885G>A		intron_variant	Intron 4 of 9		XP_016866419.1
LGSN	XM_047418866.1	c.-288+4885G>A		intron_variant	Intron 6 of 11		XP_047274822.1
LGSN	XM_011535892.4	c.-303+4885G>A		intron_variant	Intron 4 of 9		XP_011534194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000825519.1	n.1748G>A		non_coding_transcript_exon_variant	Exon 7 of 7
ENSG00000289911	ENST00000825503.1	n.306-23570G>A		intron_variant	Intron 3 of 3
ENSG00000289911	ENST00000825504.1	n.683+4885G>A		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18376 AN: 152018 Hom.: 2433 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.0974

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0968

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

GnomAD4 genome AF: 0.121 AC: 18427 AN: 152136 Hom.: 2443 Cov.: 32 AF XY: 0.118 AC XY: 8762 AN XY: 74384

African (AFR) AF: 0.334 AC: 13831 AN: 41444

American (AMR) AF: 0.0689 AC: 1053 AN: 15292

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

East Asian (EAS) AF: 0.0976 AC: 506 AN: 5184

South Asian (SAS) AF: 0.0707 AC: 341 AN: 4826

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10602

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2051 AN: 68002

Other (OTH) AF: 0.0972 AC: 205 AN: 2108

Alfa AF: 0.0746 Hom.: 272

Bravo AF: 0.134

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs1525354; hg19: chr6-64084316;