rs9449291

Variant names:

• chr6-63453048-G-A
• rs9449291
• ENST00000701584.1:n.134-9290C>T

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.134-9290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,814 control chromosomes in the GnomAD database, including 17,916 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 0.46 (17916 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-963-9290C>T		intron_variant	Intron 1 of 11		XP_047274822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000701584.1	n.134-9290C>T		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825503.1	n.131-9290C>T		intron_variant	Intron 1 of 3
ENSG00000289911	ENST00000825504.1	n.146-9290C>T		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825505.1	n.93-9290C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69966 AN: 151696 Hom.: 17924 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.461 AC: 69959 AN: 151814 Hom.: 17916 Cov.: 32 AF XY: 0.465 AC XY: 34463 AN XY: 74178

African (AFR) AF: 0.227 AC: 9406 AN: 41376

American (AMR) AF: 0.462 AC: 7046 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2753 AN: 5166

South Asian (SAS) AF: 0.521 AC: 2508 AN: 4814

European-Finnish (FIN) AF: 0.611 AC: 6401 AN: 10478

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38001 AN: 67940

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.496 Hom.: 2947

Bravo AF: 0.438

Asia WGS AF: 0.550 AC: 1896 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.22
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs9449291; hg19: chr6-64162953;