chr6-63443786-G-A

Variant names:

• chr6-63443786-G-A
• rs2076874

Variant summary

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

The variant allele was found at a frequency of 0.582 in 151,880 control chromosomes in the GnomAD database, including 25,976 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 0.58 (25976 hom., cov: 30)
• Consequence: LOC642554 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 2 publications found

Genes affected

LOC642554 (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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 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.134-28C>T		intron	N/A
	ENSG00000289911	ENST00000825503.1		n.131-28C>T		intron	N/A
	ENSG00000289911	ENST00000825504.1		n.146-28C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88332 AN: 151762 Hom.: 25965 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.582 AC: 88386 AN: 151880 Hom.: 25976 Cov.: 30 AF XY: 0.586 AC XY: 43497 AN XY: 74228

African (AFR) AF: 0.595 AC: 24648 AN: 41392

American (AMR) AF: 0.534 AC: 8141 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2261 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3037 AN: 5162

South Asian (SAS) AF: 0.609 AC: 2933 AN: 4814

European-Finnish (FIN) AF: 0.669 AC: 7060 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38358 AN: 67922

Other (OTH) AF: 0.598 AC: 1264 AN: 2112

Alfa AF: 0.575 Hom.: 3107

Bravo AF: 0.571

Asia WGS AF: 0.634 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.20
PhyloP100		-0.99

Splicing

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

Other links and lift over

dbSNP: rs2076874; hg19: chr6-64153691;