Genetic Variant LGALS9:c.759-38T>C (chr17-27647232-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200

Publications

23 publications found

Variant links:

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]

LGALS9 links:

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new If you want to explore the variant's impact on the transcript NM_009587.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_009587.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LGALS9	NM_009587.3	MANE Select	c.759-38T>C	intron	N/A	NP_033665.1	O00182-1
LGALS9	NM_002308.4		c.663-38T>C	intron	N/A	NP_002299.2	O00182-2
LGALS9	NM_001330163.2		c.662+114T>C	intron	N/A	NP_001317092.1	O00182-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LGALS9	ENST00000395473.7	TSL:1 MANE Select	c.759-38T>C	intron	N/A	ENSP00000378856.2	O00182-1
LGALS9	ENST00000302228.9	TSL:1	c.663-38T>C	intron	N/A	ENSP00000306228.5	O00182-2
LGALS9	ENST00000481514.5	TSL:1	n.1468-38T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50030

AN:

151884

Hom.:

8502

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.359

AC:

90095

AN:

250744

AF XY:

0.361

show subpopulations

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 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.:

AF XY:

0.363

AC XY:

264104

AN XY:

726776

show subpopulations

African (AFR)

AF:

0.232

AC:

7772

AN:

33462

American (AMR)

AF:

0.426

AC:

19033

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

10647

AN:

26134

East Asian (EAS)

AF:

0.305

AC:

12090

AN:

39692

South Asian (SAS)

AF:

0.372

AC:

32082

AN:

86218

European-Finnish (FIN)

AF:

0.325

AC:

17372

AN:

53392

Middle Eastern (MID)

AF:

0.432

AC:

2241

AN:

5188

European-Non Finnish (NFE)

AF:

0.367

AC:

407714

AN:

1111854

Other (OTH)

AF:

0.362

AC:

21814

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

23141

46283

69424

92566

115707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12908

25816

38724

51632

64540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.329

AC:

50057

AN:

152002

Hom.:

8509

Cov.:

AF XY:

0.327

AC XY:

24267

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.232

AC:

9624

AN:

41450

American (AMR)

AF:

0.407

AC:

6216

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1374

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1450

AN:

5144

South Asian (SAS)

AF:

0.372

AC:

1791

AN:

4820

European-Finnish (FIN)

AF:

0.332

AC:

3508

AN:

10564

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24891

AN:

67956

Other (OTH)

AF:

0.361

AC:

763

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1668

3337

5005

6674

8342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.362

Hom.:

14335

Bravo

AF:

0.332

Asia WGS

AF:

0.322

AC:

1119

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.35

PhyloP100

0.020

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over