rs1009977

Positions:

• chr14-55136284-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002306.4(LGALS3):​c.-4-1086T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,602 control chromosomes in the GnomAD database, including 18,507 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 0.48 (18507 hom., cov: 30)
• Consequence: LGALS3 NM_002306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS3	NM_002306.4	c.-4-1086T>G		intron_variant		ENST00000254301.14
LGALS3	NM_001357678.2	c.39-1086T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS3	ENST00000254301.14	c.-4-1086T>G		intron_variant		1	NM_002306.4	P1
LGALS3	ENST00000553493.5	c.-4-1086T>G		intron_variant		3
LGALS3	ENST00000554715.1	c.-4-1086T>G		intron_variant		3
LGALS3	ENST00000553755.5	n.46-1761T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72247 AN: 151484 Hom.: 18470 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.477 AC: 72334 AN: 151602 Hom.: 18507 Cov.: 30 AF XY: 0.476 AC XY: 35264 AN XY: 74042

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.420

Alfa AF: 0.408 Hom.: 13065

Bravo AF: 0.467

Asia WGS AF: 0.381 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.58

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: rs1009977; hg19: chr14-55603002;