dbSNP rs4557499: LGSN:c.-963-36884C>A (chr6-63480642-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_047418866.1(LGSN):c.-963-36884C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,716 control chromosomes in the GnomAD database, including 18,203 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 ( 18188 hom., cov: 30)

Exomes 𝑓: 0.67 ( 15 hom. )

Consequence

LGSN
XM_047418866.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

Variant links:

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]

LGSN links:

EEF1B2P5 (HGNC:32476): (eukaryotic translation elongation factor 1 beta 2 pseudogene 5)

EEF1B2P5 links:

ENSG00000289911 (HGNC:):

ENSG00000289911 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGSN	XM_047418866.1 link	c.-963-36884C>A		intron_variant	Intron 1 of 11		XP_047274822.1
EEF1B2P5		n.63480642G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1B2P5	ENST00000444820.2 link	n.447+62G>T		intron_variant	Intron 1 of 1	6
ENSG00000289911	ENST00000701584.1 link	n.134-36884C>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70479

AN:

151528

Hom.:

18197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.671

AC:

AN:

Hom.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.729

Gnomad4 NFE exome

AF:

0.643

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.465

AC:

70474

AN:

151646

Hom.:

18188

Cov.:

AF XY:

0.469

AC XY:

34722

AN XY:

74094

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.465

Gnomad4 ASJ

AF:

0.637

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.506

Alfa

AF:

0.500

Hom.:

2978

Bravo

AF:

0.443

Asia WGS

AF:

0.547

AC:

1903

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.4

DANN

Benign

0.88

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over