rs10498474

Variant names:

• chr14-55144136-A-G
• rs10498474
• NM_002306.4:c.598-980A>G

Variant summary

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

The NM_002306.4(LGALS3):​c.598-980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 152,160 control chromosomes in the GnomAD database, including 1,393 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 0.083 (1393 hom., cov: 33)
• Consequence: LGALS3 NM_002306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 2 publications found

Genes affected

LGALS3 (HGNC:6563): (galectin 3) This gene encodes a member of the galectin family of carbohydrate binding proteins. Members of this protein family have an affinity for beta-galactosides. The encoded protein is characterized by an N-terminal proline-rich tandem repeat domain and a single C-terminal carbohydrate recognition domain. This protein can self-associate through the N-terminal domain allowing it to bind to multivalent saccharide ligands. This protein localizes to the extracellular matrix, the cytoplasm and the nucleus. This protein plays a role in numerous cellular functions including apoptosis, innate immunity, cell adhesion and T-cell regulation. The protein exhibits antimicrobial activity against bacteria and fungi. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002306.4. 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
	LGALS3	NM_002306.4	MANE Select	c.598-980A>G		intron	N/A	NP_002297.2	P17931
	LGALS3	NM_001357678.2		c.640-980A>G		intron	N/A	NP_001344607.1
	LGALS3	NR_003225.2		n.1642-980A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS3	ENST00000254301.14	TSL:1 MANE Select	c.598-980A>G		intron	N/A	ENSP00000254301.9	P17931
	LGALS3	ENST00000556438.6	TSL:1	n.1437-980A>G		intron	N/A
	LGALS3	ENST00000947958.1		c.739-980A>G		intron	N/A	ENSP00000618017.1

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12522 AN: 152042 Hom.: 1384 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0589

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.00794

Gnomad OTH AF: 0.0704

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

GnomAD4 genome AF: 0.0825 AC: 12558 AN: 152160 Hom.: 1393 Cov.: 33 AF XY: 0.0803 AC XY: 5977 AN XY: 74420

African (AFR) AF: 0.246 AC: 10225 AN: 41484

American (AMR) AF: 0.0446 AC: 681 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0589 AC: 204 AN: 3466

East Asian (EAS) AF: 0.0647 AC: 335 AN: 5176

South Asian (SAS) AF: 0.0676 AC: 326 AN: 4826

European-Finnish (FIN) AF: 0.00518 AC: 55 AN: 10610

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.00794 AC: 540 AN: 67998

Other (OTH) AF: 0.0744 AC: 157 AN: 2110

Alfa AF: 0.0601 Hom.: 140

Bravo AF: 0.0918

Asia WGS AF: 0.0830 AC: 286 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	4.6
DANN	Benign	0.62
PhyloP100		0.12
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: rs10498474; hg19: chr14-55610854;