6-63375082-T-G

Variant names:

• chr6-63375082-T-G
• rs2753070
• XM_017010930.3:c.-288+4214A>C

Variant summary

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

The ENST00000825503.1(ENSG00000289911):​n.306-24241A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,254 control chromosomes in the GnomAD database, including 2,476 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 0.12 (2476 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000825503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 1 publications found

Genes affected

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]

ENSG00000289911 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000825503.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289911	ENST00000825503.1		n.306-24241A>C		intron	N/A
	ENSG00000289911	ENST00000825504.1		n.683+4214A>C		intron	N/A
	ENSG00000289911	ENST00000825506.1		n.1095+4214A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18468 AN: 152136 Hom.: 2462 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.122 AC: 18527 AN: 152254 Hom.: 2476 Cov.: 32 AF XY: 0.118 AC XY: 8807 AN XY: 74460

African (AFR) AF: 0.336 AC: 13936 AN: 41504

American (AMR) AF: 0.0690 AC: 1057 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.0973 AC: 505 AN: 5192

South Asian (SAS) AF: 0.0713 AC: 344 AN: 4828

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2041 AN: 68020

Other (OTH) AF: 0.0971 AC: 205 AN: 2112

Alfa AF: 0.0544 Hom.: 193

Bravo AF: 0.134

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.32
PhyloP100		-1.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2753070;

hg19: chr6-64084987;