chr1-236542934-A-G

Variant names:

• chr1-236542934-A-G
• rs35968435
• ENST00000450372.6:c.569A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006499.5(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. 13/19 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 NM_006499.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.26
• Publications: 8 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]

ENSG00000230325 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006499.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	NM_201544.4	MANE Select	c.549+147A>G		intron	N/A	NP_963838.1	O00214-1
	LGALS8	NM_006499.5		c.569A>G	p.Asp190Gly	missense	Exon 9 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.569A>G	p.Asp190Gly	missense	Exon 9 of 12	NP_963839.1	O00214-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000450372.6	TSL:1	c.569A>G	p.Asp190Gly	missense	Exon 9 of 12	ENSP00000408657.2	O00214-2
	LGALS8	ENST00000525042.1	TSL:1	c.392A>G	p.Asp131Gly	missense	Exon 5 of 8	ENSP00000431884.1	F6V2D4
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.549+147A>G		intron	N/A	ENSP00000355543.4	O00214-1

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

GnomAD2 exomes AF: 0.00682 AC: 1715 AN: 251478 AF XY: 0.00479

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 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

African (AFR) AF: 0.0926 AC: 3100 AN: 33470

American (AMR) AF: 0.00572 AC: 256 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53420

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5768

European-Non Finnish (NFE) AF: 0.000285 AC: 317 AN: 1111992

Other (OTH) AF: 0.00714 AC: 431 AN: 60396

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

African (AFR) AF: 0.0896 AC: 3718 AN: 41518

American (AMR) AF: 0.0109 AC: 167 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68032

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.00948 Hom.: 124

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.90	T
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.073
Sift	Benign	0.13	T
Sift4G	Benign	0.44	T
Polyphen		0.88	P
Vest4		0.39
MVP		0.44
MPC		0.082
ClinPred		0.014	T
GERP RS		4.1
gMVP		0.38
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35968435; hg19: chr1-236706234;