6-63476127-G-A

Variant names:

• chr6-63476127-G-A
• rs9353016
• ENST00000701584.1:n.134-32369C>T

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.134-32369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,946 control chromosomes in the GnomAD database, including 18,196 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 (18196 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 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	ENST00000701584.1		n.134-32369C>T		intron	N/A
	ENSG00000289911	ENST00000825503.1		n.131-32369C>T		intron	N/A
	ENSG00000289911	ENST00000825504.1		n.146-32369C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70534 AN: 151828 Hom.: 18205 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.464 AC: 70529 AN: 151946 Hom.: 18196 Cov.: 32 AF XY: 0.468 AC XY: 34757 AN XY: 74250

African (AFR) AF: 0.228 AC: 9469 AN: 41444

American (AMR) AF: 0.464 AC: 7067 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2205 AN: 3464

East Asian (EAS) AF: 0.549 AC: 2837 AN: 5166

South Asian (SAS) AF: 0.513 AC: 2473 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6517 AN: 10552

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.564 AC: 38324 AN: 67952

Other (OTH) AF: 0.505 AC: 1065 AN: 2110

Alfa AF: 0.529 Hom.: 70575

Bravo AF: 0.443

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.39
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs9353016; hg19: chr6-64186032;