rs2677023

Variant names:

• chr6-63373555-G-A
• rs2677023
• ENST00000825503.1:n.306-22714C>T

Variant summary

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

The ENST00000825503.1(ENSG00000289911):​n.306-22714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,100 control chromosomes in the GnomAD database, including 2,447 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 (2447 hom., cov: 32)
• Consequence: ENSG00000289911 ENST00000825503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_017010930.3	c.-288+5741C>T		intron_variant	Intron 4 of 9		XP_016866419.1
LGSN	XM_047418866.1	c.-288+5741C>T		intron_variant	Intron 6 of 11		XP_047274822.1
LGSN	XM_011535892.4	c.-303+5741C>T		intron_variant	Intron 4 of 9		XP_011534194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289911	ENST00000825503.1	n.306-22714C>T		intron_variant	Intron 3 of 3
ENSG00000289911	ENST00000825504.1	n.683+5741C>T		intron_variant	Intron 5 of 5
ENSG00000289911	ENST00000825506.1	n.1095+5741C>T		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18369 AN: 151982 Hom.: 2434 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.121 AC: 18425 AN: 152100 Hom.: 2447 Cov.: 32 AF XY: 0.118 AC XY: 8760 AN XY: 74362

African (AFR) AF: 0.334 AC: 13844 AN: 41422

American (AMR) AF: 0.0688 AC: 1052 AN: 15288

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

East Asian (EAS) AF: 0.0968 AC: 502 AN: 5184

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4826

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2038 AN: 68004

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.0781 Hom.: 219

Bravo AF: 0.134

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.75
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs2677023; hg19: chr6-64083460;