rs114214013

Variant names:

• chr1-236543613-C-T
• rs114214013
• NM_201544.4:c.603C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_201544.4(LGALS8):​c.603C>T​(p.Val201Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,984 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (12 hom.)
• Consequence: LGALS8 NM_201544.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.720
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-236543613-C-T is Benign according to our data. Variant chr1-236543613-C-T is described in ClinVar as Benign. ClinVar VariationId is 721142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.72 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00128 (1874/1461766) while in subpopulation EAS AF = 0.0194 (769/39700). AF 95% confidence interval is 0.0182. There are 12 homozygotes in GnomAdExome4. There are 891 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	NM_201544.4	MANE Select	c.603C>T	p.Val201Val	synonymous	Exon 8 of 10	NP_963838.1	O00214-1
	LGALS8	NM_006499.5		c.729C>T	p.Val243Val	synonymous	Exon 10 of 12	NP_006490.3
	LGALS8	NM_201545.2		c.729C>T	p.Val243Val	synonymous	Exon 10 of 12	NP_963839.1	O00214-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.603C>T	p.Val201Val	synonymous	Exon 8 of 10	ENSP00000355543.4	O00214-1
	LGALS8	ENST00000450372.6	TSL:1	c.729C>T	p.Val243Val	synonymous	Exon 10 of 12	ENSP00000408657.2	O00214-2
	LGALS8	ENST00000341872.10	TSL:1	c.603C>T	p.Val201Val	synonymous	Exon 9 of 11	ENSP00000342139.6	O00214-1

Frequencies

GnomAD3 genomes AF: 0.00454 AC: 691 AN: 152100 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00261 AC: 656 AN: 251472 AF XY: 0.00221

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0160

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00128 AC: 1874 AN: 1461766 Hom.: 12 Cov.: 33 AF XY: 0.00123 AC XY: 891 AN XY: 727178

African (AFR) AF: 0.0145 AC: 487 AN: 33476

American (AMR) AF: 0.00114 AC: 51 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.0194 AC: 769 AN: 39700

South Asian (SAS) AF: 0.000916 AC: 79 AN: 86252

European-Finnish (FIN) AF: 0.000880 AC: 47 AN: 53418

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000243 AC: 270 AN: 1111902

Other (OTH) AF: 0.00255 AC: 154 AN: 60390

GnomAD4 genome AF: 0.00457 AC: 695 AN: 152218 Hom.: 4 Cov.: 32 AF XY: 0.00423 AC XY: 315 AN XY: 74434

African (AFR) AF: 0.0136 AC: 565 AN: 41526

American (AMR) AF: 0.00105 AC: 16 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5170

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68010

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00309 Hom.: 2

Bravo AF: 0.00478

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.65
DANN	Benign	0.87
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs114214013; hg19: chr1-236706913; COSMIC: COSV53024827; COSMIC: COSV53024827;