rs4659682

Variant names:

• chr1-236518948-A-G
• rs4659682
• NM_201545.2:c.-104+448A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201545.2(LGALS8):​c.-104+448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,994 control chromosomes in the GnomAD database, including 30,393 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 0.62 (30393 hom., cov: 32)
• Consequence: LGALS8 NM_201545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 7 publications found

Genes affected

LGALS8 (HGNC:6569): (galectin 8) This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201545.2. 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
	LGALS8	NM_201545.2		c.-104+448A>G		intron	N/A	NP_963839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000352231.6	TSL:2	c.-104+448A>G		intron	N/A	ENSP00000309576.2
	LGALS8	ENST00000526589.5	TSL:5	c.-432+448A>G		intron	N/A	ENSP00000435460.1
	LGALS8	ENST00000527974.5	TSL:5	c.-104+664A>G		intron	N/A	ENSP00000431398.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94807 AN: 151876 Hom.: 30380 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.614

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.624 AC: 94859 AN: 151994 Hom.: 30393 Cov.: 32 AF XY: 0.630 AC XY: 46765 AN XY: 74278

African (AFR) AF: 0.477 AC: 19743 AN: 41404

American (AMR) AF: 0.695 AC: 10597 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2212 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4694 AN: 5192

South Asian (SAS) AF: 0.726 AC: 3497 AN: 4818

European-Finnish (FIN) AF: 0.691 AC: 7281 AN: 10542

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44705 AN: 67996

Other (OTH) AF: 0.615 AC: 1297 AN: 2110

Alfa AF: 0.652 Hom.: 60293

Bravo AF: 0.621

Asia WGS AF: 0.762 AC: 2651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.50
PhyloP100		-0.35
Mutation Taster		=100/0	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: rs4659682; hg19: chr1-236682248; COSMIC: COSV53024036; COSMIC: COSV53024036;