rs1126407

chr1-236537507-T-Achr1-236537507-T-C

Variant summary

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

The NM_201544.4(LGALS8):c.56T>A(p.Phe19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,564,154 control chromosomes in the GnomAD database, including 347,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.61 (29286 hom., cov: 32)
  • Exomes 𝑓: 0.66 (318179 hom.)
• Consequence: LGALS8 NM_201544.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

LGALS8 (HGNC:6569): (galectin 8) This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5207125E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS8	NM_201544.4	c.56T>A	p.Phe19Tyr	missense_variant	3/10	ENST00000366584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS8	ENST00000366584.9	c.56T>A	p.Phe19Tyr	missense_variant	3/10	1	NM_201544.4	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92806 AN: 151824 Hom.: 29267 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.607

GnomAD3 exomes AF: 0.611 AC: 152862 AN: 250140 Hom.: 48131 AF XY: 0.610 AC XY: 82517 AN XY: 135244

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.486

Gnomad SAS exome AF: 0.472

Gnomad FIN exome AF: 0.736

Gnomad NFE exome AF: 0.686

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.664 AC: 937110 AN: 1412210 Hom.: 318179 Cov.: 31 AF XY: 0.658 AC XY: 464228 AN XY: 705084

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.533

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.739

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.611 AC: 92872 AN: 151944 Hom.: 29286 Cov.: 32 AF XY: 0.608 AC XY: 45190 AN XY: 74268

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.605

Alfa AF: 0.665 Hom.: 25638

Bravo AF: 0.591

TwinsUK AF: 0.701 AC: 2598

ALSPAC AF: 0.693 AC: 2672

ESP6500AA AF: 0.493 AC: 2173

ESP6500EA AF: 0.683 AC: 5870

ExAC AF: 0.609 AC: 73977

Asia WGS AF: 0.452 AC: 1576 AN: 3478

EpiCase AF: 0.673

EpiControl AF: 0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	14
Dann	Benign	0.77
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.22	T;T;.;T;.;T;.;T;.;T;T;.;T;T;T;.
MetaRNN	Benign	0.0000045	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.29	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.89	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.0010	.;.;B;.;B;.;B;.;B;B;B;B;.;.;B;B
Vest4		0.098, 0.13, 0.10, 0.14, 0.17, 0.10, 0.14, 0.13, 0.14, 0.12
MPC		0.060
ClinPred		0.0080	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.84

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: rs1126407; hg19: chr1-236700807; COSMIC: COSV53023494; COSMIC: COSV53023494;