rs4985834

Variant names:

• chr17-20467454-G-C
• rs4985834
• NM_001367292.2:c.17C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-20467454-G-C
• chr17-20467454-G-A
• chr17-20467454-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.471
• Publications: 14 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367292.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9B	NM_001367292.2	MANE Select	c.17C>G	p.Ser6Cys	missense	Exon 1 of 11	NP_001354221.1	Q3B8N2-1
	LGALS9B	NM_001042685.3		c.17C>G	p.Ser6Cys	missense	Exon 1 of 11	NP_001036150.1	Q3B8N2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9B	ENST00000423676.8	TSL:1 MANE Select	c.17C>G	p.Ser6Cys	missense	Exon 1 of 11	ENSP00000388841.3	Q3B8N2-1
	LGALS9B	ENST00000324290.5	TSL:5	c.17C>G	p.Ser6Cys	missense	Exon 1 of 11	ENSP00000315564.5	Q3B8N2-2
	LGALS9B	ENST00000897463.1		c.17C>G	p.Ser6Cys	missense	Exon 1 of 10	ENSP00000567522.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 36983 AN: 46382 Hom.: 15372 Cov.: 7

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

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.: 6 AF XY: 0.733 AC XY: 143814 AN XY: 196282

⚠️ 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.

GnomAD4 genome AF: 0.797 AC: 36997 AN: 46404 Hom.: 15379 Cov.: 7 AF XY: 0.787 AC XY: 16896 AN XY: 21462

⚠️ 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: 91 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.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.772 AC: 37863

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.3
DANN	Benign	0.73
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.47
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.015
Sift	Benign	0.086	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.062
ClinPred		0.0073	T
GERP RS		-0.15
PromoterAI		-0.063	Neutral
Varity_R		0.066
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4985834; hg19: chr17-20370767; COSMIC: COSV60864317;