rs10498474

Positions:

• chr14-55144136-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LGALS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS3	NM_002306.4	c.598-980A>G		intron_variant		ENST00000254301.14	NP_002297.2
LGALS3	NM_001357678.2	c.640-980A>G		intron_variant			NP_001344607.1
LGALS3	NR_003225.2	n.1642-980A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS3	ENST00000254301.14	c.598-980A>G		intron_variant		1	NM_002306.4	ENSP00000254301.9
LGALS3	ENST00000556438.6	n.1437-980A>G		intron_variant		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

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.0589

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.0676

Gnomad4 FIN AF: 0.00518

Gnomad4 NFE AF: 0.00794

Gnomad4 OTH AF: 0.0744

Alfa AF: 0.0533 Hom.: 117

Bravo AF: 0.0918

Asia WGS AF: 0.0830 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs10498474; hg19: chr14-55610854;