17-20467454-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001367292.2(LGALS9B):c.17C>G(p.Ser6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 15379 hom., cov: 7)

Exomes 𝑓: 0.72 ( 120350 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9B
NM_001367292.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.471

Publications

14 publications found

Variant links:

Genes affected

LGALS9B (HGNC:24842): (galectin 9B) This gene was initially thought to represent a pseudogene of galectin 9; however, this transcript has good exon-intron structure and encodes a predicted protein of the same size as and highly similar to galectin 9. This gene is one of two similar loci on chromosome 17p similar to galectin 9 and now thought to be protein-encoding. This gene is the more centromeric gene. [provided by RefSeq, Jul 2008]

LGALS9B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.35666E-6).

BP6

Variant 17-20467454-G-C is Benign according to our data. Variant chr17-20467454-G-C is described in ClinVar as Benign. ClinVar VariationId is 403031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 15379 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 link	c.17C>G	p.Ser6Cys	missense_variant	Exon 1 of 11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 link	c.17C>G	p.Ser6Cys	missense_variant	Exon 1 of 11		NP_001036150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
LGALS9B	ENST00000423676.8 link	c.17C>G	p.Ser6Cys	missense_variant	Exon 1 of 11	1	NM_001367292.2	ENSP00000388841.3
LGALS9B	ENST00000324290.5 link	c.17C>G	p.Ser6Cys	missense_variant	Exon 1 of 11	5		ENSP00000315564.5
LGALS9B	ENST00000578481.5 link	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000464627.1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

36983

AN:

46382

Hom.:

15372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.859

Gnomad FIN

AF:

0.882

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.805

GnomAD2 exomes

AF:

0.834

AC:

50177

AN:

60144

AF XY:

0.838

show subpopulations

Gnomad AFR exome

AF:

0.815

Gnomad AMR exome

AF:

0.745

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.936

Gnomad NFE exome

AF:

0.931

Gnomad OTH exome

AF:

0.882

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.724

AC:

279969

AN:

386744

Hom.:

120350

Cov.:

AF XY:

0.733

AC XY:

143814

AN XY:

196282

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.521

AC:

3330

AN:

6388

American (AMR)

AF:

0.596

AC:

7918

AN:

13294

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

7148

AN:

9030

East Asian (EAS)

AF:

0.332

AC:

6204

AN:

18670

South Asian (SAS)

AF:

0.822

AC:

18394

AN:

22386

European-Finnish (FIN)

AF:

0.909

AC:

26798

AN:

29472

Middle Eastern (MID)

AF:

0.806

AC:

1049

AN:

1302

European-Non Finnish (NFE)

AF:

0.730

AC:

195366

AN:

267754

Other (OTH)

AF:

0.746

AC:

13762

AN:

18448

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.327

Heterozygous variant carriers

2351

4702

7053

9404

11755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2498

4996

7494

9992

12490

<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:

0.797

AC:

36997

AN:

46404

Hom.:

15379

Cov.:

AF XY:

0.787

AC XY:

16896

AN XY:

21462

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.673

AC:

5382

AN:

7992

American (AMR)

AF:

0.728

AC:

3172

AN:

4356

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

1246

AN:

1446

East Asian (EAS)

AF:

0.392

AC:

778

AN:

1984

South Asian (SAS)

AF:

0.859

AC:

821

AN:

956

European-Finnish (FIN)

AF:

0.882

AC:

2533

AN:

2872

Middle Eastern (MID)

AF:

0.892

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.862

AC:

22307

AN:

25876

Other (OTH)

AF:

0.804

AC:

463

AN:

576

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

252

504

755

1007

1259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.00

Hom.:

ExAC

AF:

0.772

AC:

37863

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.3

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0057

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.18

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

-0.47

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.015

Sift

Benign

0.086

T;T

Sift4G

Benign

0.17

T;T

Vest4

0.062

ClinPred

0.0073

GERP RS

-0.15

PromoterAI

-0.063

Neutral

(source)

Varity_R

0.066

gMVP

0.15

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over