chr1-236537507-T-A

Variant names:

• chr1-236537507-T-A
• rs1126407
• NM_201544.4:c.56T>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 0.61 (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
• Publications: 42 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=4.5207125E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 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.56T>A	p.Phe19Tyr	missense	Exon 3 of 10	NP_963838.1
	LGALS8	NM_006499.5		c.56T>A	p.Phe19Tyr	missense	Exon 4 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.56T>A	p.Phe19Tyr	missense	Exon 4 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.56T>A	p.Phe19Tyr	missense	Exon 3 of 10	ENSP00000355543.4
	LGALS8	ENST00000450372.6	TSL:1	c.56T>A	p.Phe19Tyr	missense	Exon 4 of 12	ENSP00000408657.2
	LGALS8	ENST00000341872.10	TSL:1	c.56T>A	p.Phe19Tyr	missense	Exon 4 of 11	ENSP00000342139.6

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

GnomAD2 exomes AF: 0.611 AC: 152862 AN: 250140 AF XY: 0.610

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.484 AC: 15754 AN: 32572

American (AMR) AF: 0.533 AC: 23751 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 15461 AN: 25824

East Asian (EAS) AF: 0.472 AC: 18636 AN: 39454

South Asian (SAS) AF: 0.478 AC: 40736 AN: 85286

European-Finnish (FIN) AF: 0.739 AC: 39409 AN: 53314

Middle Eastern (MID) AF: 0.541 AC: 3064 AN: 5668

European-Non Finnish (NFE) AF: 0.696 AC: 742892 AN: 1066822

Other (OTH) AF: 0.637 AC: 37407 AN: 58738

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.494 AC: 20467 AN: 41394

American (AMR) AF: 0.574 AC: 8770 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2111 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2503 AN: 5166

South Asian (SAS) AF: 0.459 AC: 2214 AN: 4826

European-Finnish (FIN) AF: 0.751 AC: 7919 AN: 10546

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46920 AN: 67952

Other (OTH) AF: 0.605 AC: 1274 AN: 2106

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 v4.9

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
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0000045	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.72	N
PhyloP100		2.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.098
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
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: rs1126407; hg19: chr1-236700807; COSMIC: COSV53023494; COSMIC: COSV53023494;