6-63466542-T-C

Variant names:

• chr6-63466542-T-C
• rs6942342
• ENST00000701584.1:n.134-22784A>G

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.134-22784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,066 control chromosomes in the GnomAD database, including 18,256 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 (18256 hom., cov: 33)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1	c.-963-22784A>G		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.134-22784A>G		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825503.1	n.131-22784A>G		intron_variant	Intron 1 of 3
ENSG00000289911	ENST00000825504.1	n.146-22784A>G		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825505.1	n.93-22784A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70645 AN: 151948 Hom.: 18265 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.465 AC: 70635 AN: 152066 Hom.: 18256 Cov.: 33 AF XY: 0.468 AC XY: 34791 AN XY: 74340

African (AFR) AF: 0.228 AC: 9456 AN: 41492

American (AMR) AF: 0.464 AC: 7085 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2212 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2813 AN: 5164

South Asian (SAS) AF: 0.517 AC: 2487 AN: 4814

European-Finnish (FIN) AF: 0.617 AC: 6518 AN: 10562

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38423 AN: 67990

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.508 Hom.: 2604

Bravo AF: 0.442

Asia WGS AF: 0.546 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs6942342; hg19: chr6-64176447;