6-63459629-A-C

Variant names:

• chr6-63459629-A-C
• rs9449312
• ENST00000701584.1:n.134-15871T>G

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.134-15871T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,610 control chromosomes in the GnomAD database, including 22,255 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 0.54 (22255 hom., cov: 29)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289911	ENST00000701584.1		n.134-15871T>G		intron	N/A
	ENSG00000289911	ENST00000825503.1		n.131-15871T>G		intron	N/A
	ENSG00000289911	ENST00000825504.1		n.146-15871T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81544 AN: 151492 Hom.: 22249 Cov.: 29

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.538 AC: 81585 AN: 151610 Hom.: 22255 Cov.: 29 AF XY: 0.539 AC XY: 39887 AN XY: 74032

African (AFR) AF: 0.475 AC: 19643 AN: 41322

American (AMR) AF: 0.493 AC: 7487 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2712 AN: 5114

South Asian (SAS) AF: 0.545 AC: 2614 AN: 4794

European-Finnish (FIN) AF: 0.618 AC: 6480 AN: 10490

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38655 AN: 67922

Other (OTH) AF: 0.560 AC: 1182 AN: 2110

Alfa AF: 0.559 Hom.: 64139

Bravo AF: 0.526

Asia WGS AF: 0.583 AC: 2031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.086
DANN	Benign	0.72
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs9449312; hg19: chr6-64169534;