rs4644

Variant names:

• chr14-55138217-C-A
• rs4644
• NM_002306.4:c.191C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-55138217-C-A
• chr14-55138217-C-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.191C>A​(p.Pro64His) variant causes a missense change. The variant allele was found at a frequency of 0.389 in 1,613,016 control chromosomes in the GnomAD database, including 125,766 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 0.36 (10258 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115508 hom.)
• Consequence: LGALS3 NM_002306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• Publications: 107 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 (MetaRNN=0.0030170083).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS3	NM_002306.4	c.191C>A	p.Pro64His	missense_variant	Exon 3 of 6	ENST00000254301.14	NP_002297.2
LGALS3	NM_001357678.2	c.233C>A	p.Pro78His	missense_variant	Exon 4 of 7		NP_001344607.1
LGALS3	NR_003225.2	n.1235C>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS3	ENST00000254301.14	c.191C>A	p.Pro64His	missense_variant	Exon 3 of 6	1	NM_002306.4	ENSP00000254301.9

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54259 AN: 151874 Hom.: 10247 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.351 AC: 86468 AN: 246424 AF XY: 0.358

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.192

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.393 AC: 573600 AN: 1461024 Hom.: 115508 Cov.: 52 AF XY: 0.392 AC XY: 284784 AN XY: 726828

African (AFR) AF: 0.271 AC: 9068 AN: 33478

American (AMR) AF: 0.224 AC: 10027 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 7027 AN: 26128

East Asian (EAS) AF: 0.222 AC: 8790 AN: 39684

South Asian (SAS) AF: 0.376 AC: 32431 AN: 86240

European-Finnish (FIN) AF: 0.515 AC: 27196 AN: 52856

Middle Eastern (MID) AF: 0.246 AC: 1420 AN: 5766

European-Non Finnish (NFE) AF: 0.409 AC: 455101 AN: 1111814

Other (OTH) AF: 0.373 AC: 22540 AN: 60372

GnomAD4 genome AF: 0.357 AC: 54298 AN: 151992 Hom.: 10258 Cov.: 32 AF XY: 0.360 AC XY: 26770 AN XY: 74306

African (AFR) AF: 0.280 AC: 11626 AN: 41452

American (AMR) AF: 0.305 AC: 4667 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1059 AN: 5148

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4822

European-Finnish (FIN) AF: 0.529 AC: 5599 AN: 10594

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27608 AN: 67906

Other (OTH) AF: 0.325 AC: 685 AN: 2110

Alfa AF: 0.366 Hom.: 32730

Bravo AF: 0.332

TwinsUK AF: 0.407 AC: 1509

ALSPAC AF: 0.408 AC: 1573

ESP6500AA AF: 0.279 AC: 1015

ESP6500EA AF: 0.398 AC: 3240

ExAC AF: 0.351 AC: 42334

Asia WGS AF: 0.289 AC: 1005 AN: 3478

EpiCase AF: 0.378

EpiControl AF: 0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	.;M;.
PhyloP100		4.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-8.0	D;D;D
REVEL	Benign	0.18
Sift	Benign	0.052	T;D;D
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		1.0	.;D;.
Vest4		0.37, 0.25
MPC		0.069
ClinPred		0.11	T
GERP RS		5.7
Varity_R		0.34
gMVP		0.77
Mutation Taster		=78/22	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: rs4644; hg19: chr14-55604935; COSMIC: COSV107285615;