Variant 19-38812518-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006149.4(LGALS4):c.47C>T(p.Thr16Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,613,950 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.026 ( 169 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 156 hom. )

Consequence

LGALS4
NM_006149.4 missense, splice_region

Scores

Splicing: ADA: 0.00002393

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

LGALS4 (HGNC:6565): (galectin 4) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The expression of this gene is restricted to small intestine, colon, and rectum, and it is underexpressed in colorectal cancer. [provided by RefSeq, Jul 2008]

LGALS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022113323).

BP6

Variant 19-38812518-G-A is Benign according to our data. Variant chr19-38812518-G-A is described in ClinVar as [Benign]. Clinvar id is 777529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS4	NM_006149.4 linkuse as main transcript	c.47C>T	p.Thr16Met	missense_variant, splice_region_variant	2/10	ENST00000307751.9	NP_006140.1
LGALS4	XM_011526973.3 linkuse as main transcript	c.47C>T	p.Thr16Met	missense_variant, splice_region_variant	2/9		XP_011525275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS4	ENST00000307751.9 linkuse as main transcript	c.47C>T	p.Thr16Met	missense_variant, splice_region_variant	2/10	1	NM_006149.4	ENSP00000302100	P1

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3914

AN:

152190

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0890

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00730

AC:

1832

AN:

251118

Hom.:

AF XY:

0.00536

AC XY:

727

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.0946

Gnomad AMR exome

AF:

0.00666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00273

AC:

3985

AN:

1461642

Hom.:

156

Cov.:

AF XY:

0.00237

AC XY:

1727

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0937

Gnomad4 AMR exome

AF:

0.00678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00606

GnomAD4 genome

AF:

0.0257

AC:

3913

AN:

152308

Hom.:

169

Cov.:

AF XY:

0.0246

AC XY:

1831

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0888

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00458

Hom.:

Bravo

AF:

0.0291

ESP6500AA

AF:

0.0885

AC:

390

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00880

AC:

1068

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.28

Eigen

Benign

0.0058

Eigen_PC

Benign

-0.050

FATHMM_MKL

Uncertain

0.81

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.52

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.2

REVEL

Benign

0.064

Sift

Benign

0.14

Sift4G

Benign

0.079

Polyphen

0.96

Vest4

0.26

MVP

0.27

MPC

0.12

ClinPred

0.057

GERP RS

4.0

Varity_R

0.16

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over