17-78972027-C-G

Position:

• chr17-78972027-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000262776.8(LGALS3BP):​c.1307G>C​(p.Arg436Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,614,022 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (22 hom.)
• Consequence: LGALS3BP ENST00000262776.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.46

Genes affected

LGALS3BP (HGNC:6564): (galectin 3 binding protein) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. LGALS3BP has been found elevated in the serum of patients with cancer and in those infected by the human immunodeficiency virus (HIV). It appears to be implicated in immune response associated with natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity. Using fluorescence in situ hybridization the full length 90K cDNA has been localized to chromosome 17q25. The native protein binds specifically to a human macrophage-associated lectin known as Mac-2 and also binds galectin 1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002909094).
• BP6: Variant 17-78972027-C-G is Benign according to our data. Variant chr17-78972027-C-G is described in ClinVar as [Benign]. Clinvar id is 791457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00227 (345/152210) while in subpopulation AMR AF= 0.0167 (256/15286). AF 95% confidence interval is 0.0151. There are 2 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS3BP	NM_005567.4	c.1307G>C	p.Arg436Pro	missense_variant	6/6	ENST00000262776.8	NP_005558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS3BP	ENST00000262776.8	c.1307G>C	p.Arg436Pro	missense_variant	6/6	1	NM_005567.4	ENSP00000262776	P1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 343 AN: 152092 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00425 AC: 1067 AN: 251308 Hom.: 18 AF XY: 0.00335 AC XY: 455 AN XY: 135852

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.0246

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00511

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000651

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00139 AC: 2028 AN: 1461812 Hom.: 22 Cov.: 32 AF XY: 0.00124 AC XY: 904 AN XY: 727204

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0229

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.00413

Gnomad4 SAS exome AF: 0.000719

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000601

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152210 Hom.: 2 Cov.: 32 AF XY: 0.00262 AC XY: 195 AN XY: 74416

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.000763 Hom.: 1

Bravo AF: 0.00400

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00327 AC: 397

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000415

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.027
DANN	Benign	0.39
DEOGEN2	Benign	0.21	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.023
Sift	Benign	0.23	T
Sift4G	Benign	0.085	T
Polyphen		0.038	B
Vest4		0.19
MVP		0.067
MPC		0.22
ClinPred		0.0023	T
GERP RS		-1.1
Varity_R		0.11
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs148972972; hg19: chr17-76968109;