14-55147918-G-A

Variant names:

• chr14-55147918-G-A
• rs2274273
• ENST00000888054.1:c.*2647G>A

Variant summary

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

The ENST00000888054.1(LGALS3):​c.*2647G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,056 control chromosomes in the GnomAD database, including 12,310 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 0.40 (12310 hom., cov: 33)
• Consequence: LGALS3 ENST00000888054.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 39 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]

DLGAP5 (HGNC:16864): (DLG associated protein 5) Predicted to enable microtubule binding activity. Predicted to be involved in several processes, including centrosome localization; kinetochore assembly; and mitotic spindle organization. Located in several cellular components, including centrosome; cytosol; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000888054.1. 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
	DLGAP5	NM_014750.5	MANE Select	c.*433C>T		downstream_gene	N/A	NP_055565.3
	DLGAP5	NM_001146015.2		c.*536C>T		downstream_gene	N/A	NP_001139487.1	Q15398-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS3	ENST00000888054.1		c.*2647G>A		3_prime_UTR	Exon 6 of 6	ENSP00000558113.1
	DLGAP5	ENST00000247191.7	TSL:1 MANE Select	c.*433C>T		downstream_gene	N/A	ENSP00000247191.2	Q15398-2
	DLGAP5	ENST00000395425.6	TSL:1	c.*536C>T		downstream_gene	N/A	ENSP00000378815.2	Q15398-3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60242 AN: 151936 Hom.: 12297 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.397 AC: 60294 AN: 152056 Hom.: 12310 Cov.: 33 AF XY: 0.398 AC XY: 29595 AN XY: 74342

African (AFR) AF: 0.417 AC: 17286 AN: 41464

American (AMR) AF: 0.317 AC: 4851 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3466

East Asian (EAS) AF: 0.206 AC: 1067 AN: 5180

South Asian (SAS) AF: 0.359 AC: 1731 AN: 4822

European-Finnish (FIN) AF: 0.530 AC: 5597 AN: 10562

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27683 AN: 67968

Other (OTH) AF: 0.347 AC: 732 AN: 2108

Alfa AF: 0.388 Hom.: 32842

Bravo AF: 0.377

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		-0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2274273; hg19: chr14-55614636;