6-63379079-A-T

Variant names:

• chr6-63379079-A-T
• rs824383
• XM_017010930.3:c.-288+217T>A

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.672-6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,164 control chromosomes in the GnomAD database, including 4,010 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 0.16 (4010 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000701584.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 2 publications found

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]

ENSG00000289911 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000701584.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289911	ENST00000825505.1		n.655T>A		non_coding_transcript_exon	Exon 4 of 4
	ENSG00000289911	ENST00000825520.1		n.1608T>A		non_coding_transcript_exon	Exon 6 of 6
	ENSG00000289911	ENST00000825521.1		n.1119T>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24569 AN: 152046 Hom.: 3982 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.162 AC: 24652 AN: 152164 Hom.: 4010 Cov.: 32 AF XY: 0.161 AC XY: 11992 AN XY: 74406

African (AFR) AF: 0.406 AC: 16819 AN: 41468

American (AMR) AF: 0.226 AC: 3451 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3468

East Asian (EAS) AF: 0.115 AC: 593 AN: 5176

South Asian (SAS) AF: 0.0926 AC: 447 AN: 4826

European-Finnish (FIN) AF: 0.0260 AC: 276 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0371 AC: 2523 AN: 68022

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.00879 Hom.: 8

Bravo AF: 0.189

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.67
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs824383; hg19: chr6-64088984;