6-63404288-A-C

Variant names:

• chr6-63404288-A-C
• rs865416
• ENST00000701584.1:n.308+218T>G

Variant summary

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

The ENST00000701584.1(ENSG00000289911):​n.308+218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,116 control chromosomes in the GnomAD database, including 1,988 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 0.11 (1988 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000701584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 0 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 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.308+218T>G		intron	N/A
	ENSG00000289911	ENST00000825503.1		n.305+218T>G		intron	N/A
	ENSG00000289911	ENST00000825504.1		n.320+218T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17421 AN: 151998 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.115 AC: 17479 AN: 152116 Hom.: 1988 Cov.: 32 AF XY: 0.113 AC XY: 8382 AN XY: 74394

African (AFR) AF: 0.302 AC: 12487 AN: 41412

American (AMR) AF: 0.0767 AC: 1172 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.0615 AC: 319 AN: 5190

South Asian (SAS) AF: 0.0812 AC: 391 AN: 4818

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10620

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2407 AN: 68022

Other (OTH) AF: 0.0998 AC: 210 AN: 2104

Alfa AF: 0.0946 Hom.: 253

Bravo AF: 0.128

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.39
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs865416; hg19: chr6-64114193;