rs4239242

chr17-27647232-T-C

Variant summary

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

The NM_009587.3(LGALS9):c.759-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,612,944 control chromosomes in the GnomAD database, including 106,023 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 (8509 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97514 hom.)
• Consequence: LGALS9 NM_009587.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS9	NM_009587.3	c.759-38T>C		intron_variant		ENST00000395473.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS9	ENST00000395473.7	c.759-38T>C		intron_variant		1	NM_009587.3	P4

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50030 AN: 151884 Hom.: 8502 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.365

GnomAD3 exomes AF: 0.359 AC: 90095 AN: 250744 Hom.: 16557 AF XY: 0.361 AC XY: 48906 AN XY: 135534

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.298

Gnomad SAS exome AF: 0.372

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.363 AC: 530765 AN: 1460942 Hom.: 97514 Cov.: 57 AF XY: 0.363 AC XY: 264104 AN XY: 726776

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.362

GnomAD4 genome AF: 0.329 AC: 50057 AN: 152002 Hom.: 8509 Cov.: 32 AF XY: 0.327 AC XY: 24267 AN XY: 74304

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.361

Alfa AF: 0.366 Hom.: 11755

Bravo AF: 0.332

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4239242; hg19: chr17-25974258; COSMIC: COSV56348949; COSMIC: COSV56348949;