1-236538910-A-G

Variant names:

• chr1-236538910-A-G
• rs1041937
• NM_201544.4:c.166A>G

Variant summary

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

The NM_201544.4(LGALS8):​c.166A>G​(p.Met56Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,611,126 control chromosomes in the GnomAD database, including 408,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37413 hom., cov: 32)
  • Exomes 𝑓: 0.71 (370972 hom.)
• Consequence: LGALS8 NM_201544.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 28 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=7.61474E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201544.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	NM_201544.4	MANE Select	c.166A>G	p.Met56Val	missense	Exon 4 of 10	NP_963838.1
	LGALS8	NM_006499.5		c.166A>G	p.Met56Val	missense	Exon 5 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.166A>G	p.Met56Val	missense	Exon 5 of 12	NP_963839.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.166A>G	p.Met56Val	missense	Exon 4 of 10	ENSP00000355543.4
	LGALS8	ENST00000450372.6	TSL:1	c.166A>G	p.Met56Val	missense	Exon 5 of 12	ENSP00000408657.2
	LGALS8	ENST00000341872.10	TSL:1	c.166A>G	p.Met56Val	missense	Exon 5 of 11	ENSP00000342139.6

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106202 AN: 151764 Hom.: 37404 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.678 AC: 170168 AN: 250880 AF XY: 0.672

Gnomad AFR exome AF: 0.682

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.747

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.692

GnomAD4 exome AF: 0.710 AC: 1036725 AN: 1459246 Hom.: 370972 Cov.: 46 AF XY: 0.705 AC XY: 511732 AN XY: 726070

African (AFR) AF: 0.685 AC: 22891 AN: 33424

American (AMR) AF: 0.650 AC: 29029 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 17618 AN: 26126

East Asian (EAS) AF: 0.614 AC: 24374 AN: 39692

South Asian (SAS) AF: 0.544 AC: 46901 AN: 86148

European-Finnish (FIN) AF: 0.751 AC: 40123 AN: 53396

Middle Eastern (MID) AF: 0.656 AC: 3314 AN: 5050

European-Non Finnish (NFE) AF: 0.730 AC: 810426 AN: 1110502

Other (OTH) AF: 0.698 AC: 42049 AN: 60216

GnomAD4 genome AF: 0.700 AC: 106264 AN: 151880 Hom.: 37413 Cov.: 32 AF XY: 0.697 AC XY: 51702 AN XY: 74222

African (AFR) AF: 0.685 AC: 28408 AN: 41448

American (AMR) AF: 0.674 AC: 10266 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3269 AN: 5162

South Asian (SAS) AF: 0.529 AC: 2539 AN: 4804

European-Finnish (FIN) AF: 0.764 AC: 8050 AN: 10542

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.723 AC: 49071 AN: 67912

Other (OTH) AF: 0.708 AC: 1495 AN: 2112

Alfa AF: 0.708 Hom.: 78815

Bravo AF: 0.692

ESP6500AA AF: 0.680 AC: 2995

ESP6500EA AF: 0.707 AC: 6077

ExAC AF: 0.676 AC: 82040

Asia WGS AF: 0.594 AC: 2067 AN: 3478

EpiCase AF: 0.710

EpiControl AF: 0.703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.70
DEOGEN2	Benign	0.00091	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	7.6e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.12
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.93	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.054
ClinPred		0.0013	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.19
Mutation Taster		=100/0	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: rs1041937; hg19: chr1-236702210; COSMIC: COSV53023904; COSMIC: COSV53023904;