chr1-236542934-A-G

Position:

• chr1-236542934-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1 BP4_Strong BP6_Very_Strong BA1

The ENST00000450372.6(LGALS8):​c.569A>G​(p.Asp190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,614,106 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (169 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (163 hom.)
• Consequence: LGALS8 ENST00000450372.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.26

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• PM1: In a mutagenesis_site Does not affect localization to cytoplasmic vesicles in case of infection by S.typhimurium. (size 0) in uniprot entity LEG8_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.0021482408).
• BP6: Variant 1-236542934-A-G is Benign according to our data. Variant chr1-236542934-A-G is described in ClinVar as [Benign]. Clinvar id is 773294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS8	NM_201544.4	c.549+147A>G		intron_variant		ENST00000366584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS8	ENST00000366584.9	c.549+147A>G		intron_variant		1	NM_201544.4	P1
	ENST00000433131.1	n.142-2488T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3946 AN: 152128 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.00682 AC: 1715 AN: 251478 Hom.: 75 AF XY: 0.00479 AC XY: 651 AN XY: 135910

Gnomad AFR exome AF: 0.0900

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00286 AC: 4186 AN: 1461860 Hom.: 163 Cov.: 31 AF XY: 0.00247 AC XY: 1795 AN XY: 727240

Gnomad4 AFR exome AF: 0.0926

Gnomad4 AMR exome AF: 0.00572

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.00714

GnomAD4 genome AF: 0.0261 AC: 3967 AN: 152246 Hom.: 169 Cov.: 32 AF XY: 0.0252 AC XY: 1879 AN XY: 74450

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00470 Hom.: 53

Bravo AF: 0.0297

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0876 AC: 386

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00836 AC: 1015

Asia WGS AF: 0.00664 AC: 24 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	.;.;T;.;T;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.48	.;.;T;.;T;T;.
MetaRNN	Benign	0.0021	T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	0.65	D;D;D;D;D;D;D;D;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.43	N;N;N;N;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.13	T;T;D;T;T;T;T
Sift4G	Benign	0.44	T;T;T;T;T;T;T
Polyphen		0.88	P;P;.;P;B;P;B
Vest4		0.39
MVP		0.44
MPC		0.082
ClinPred		0.014	T
GERP RS		4.1
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs35968435; hg19: chr1-236706234;