chr6-63480642-G-T

Variant names:

• chr6-63480642-G-T
• rs4557499

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 0.465 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: EEF1B2P5 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 2 publications found

Genes affected

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

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=-0.78).
• 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
EEF1B2P5		n.63480642G>T		intragenic_variant
LGSN	XM_047418866.1	c.-963-36884C>A		intron_variant	Intron 1 of 11		XP_047274822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1B2P5	ENST00000444820.2	n.447+62G>T		intron_variant	Intron 1 of 1	6
ENSG00000289911	ENST00000701584.1	n.134-36884C>A		intron_variant	Intron 1 of 5
ENSG00000289911	ENST00000825503.1	n.131-36884C>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70479 AN: 151528 Hom.: 18197 Cov.: 30

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: 47 AN: 70 Hom.: 15 AF XY: 0.667 AC XY: 32 AN XY: 48

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.729 AC: 35 AN: 48

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.643 AC: 9 AN: 14

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.465 AC: 70474 AN: 151646 Hom.: 18188 Cov.: 30 AF XY: 0.469 AC XY: 34722 AN XY: 74094

African (AFR) AF: 0.229 AC: 9449 AN: 41342

American (AMR) AF: 0.465 AC: 7063 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2206 AN: 3464

East Asian (EAS) AF: 0.551 AC: 2830 AN: 5136

South Asian (SAS) AF: 0.513 AC: 2469 AN: 4810

European-Finnish (FIN) AF: 0.620 AC: 6499 AN: 10482

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38318 AN: 67898

Other (OTH) AF: 0.506 AC: 1068 AN: 2110

Alfa AF: 0.491 Hom.: 3001

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
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs4557499; hg19: chr6-64190547;