rs4794976

chr17-27647519-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_009587.3(LGALS9):c.921+87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,545,042 control chromosomes in the GnomAD database, including 90,819 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 0.33 (8400 hom., cov: 31)
  • Exomes 𝑓: 0.34 (82419 hom.)
• Consequence: LGALS9 NM_009587.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

LGALS9 (HGNC:6570): (galectin 9) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The protein encoded by this gene is an S-type lectin. It is overexpressed in Hodgkin's disease tissue and might participate in the interaction between the H&RS cells with their surrounding cells and might thus play a role in the pathogenesis of this disease and/or its associated immunodeficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS9	NM_009587.3	c.921+87T>G		intron_variant		ENST00000395473.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS9	ENST00000395473.7	c.921+87T>G		intron_variant		1	NM_009587.3	P4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49530 AN: 151710 Hom.: 8373 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.337 AC: 469559 AN: 1393214 Hom.: 82419 AF XY: 0.343 AC XY: 236356 AN XY: 688340

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.327 AC: 49608 AN: 151828 Hom.: 8400 Cov.: 31 AF XY: 0.332 AC XY: 24615 AN XY: 74194

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.350

Alfa AF: 0.330 Hom.: 2997

Bravo AF: 0.325

Asia WGS AF: 0.550 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.9
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4794976; hg19: chr17-25974545;