dbSNP rs34691037: GBGT1:p.Tyr232Tyr (chr9-133153925-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282629.2(GBGT1):c.677C>T(p.Thr226Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,609,570 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 163 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 140 hom. )

Consequence

GBGT1
NM_001282629.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.632

Variant links:

Genes affected

GBGT1 (HGNC:20460): (globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (FORS blood group)) This gene encodes a glycosyltransferase that plays a role in the synthesis of Forssman glycolipid (FG), a member of the globoseries glycolipid family. Glycolipids such as FG form attachment sites for the binding of pathogens to cells; expression of this protein may determine host tropism to microorganisms. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

GBGT1 links:

ENSG00000285245 (HGNC:):

ENSG00000285245 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016729832).

BP6

Variant 9-133153925-G-A is Benign according to our data. Variant chr9-133153925-G-A is described in ClinVar as [Benign]. Clinvar id is 775281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6 link	c.696C>T	p.Tyr232Tyr	synonymous_variant	Exon 7 of 7	ENST00000372040.9	NP_068836.2	Q8N5D6-1J7Q0Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBGT1	ENST00000372040.9 link	c.696C>T	p.Tyr232Tyr	synonymous_variant	Exon 7 of 7	1	NM_021996.6	ENSP00000361110.3		Q8N5D6-1
ENSG00000285245	ENST00000647146.1 link	c.396+1253C>T		intron_variant	Intron 6 of 22			ENSP00000493691.1		A0A2R8Y471

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3821

AN:

152196

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00685

AC:

1714

AN:

250390

Hom.:

AF XY:

0.00501

AC XY:

679

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0854

Gnomad AMR exome

AF:

0.00585

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000734

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00283

AC:

4121

AN:

1457256

Hom.:

140

Cov.:

AF XY:

0.00244

AC XY:

1766

AN XY:

723940

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.00648

Gnomad4 ASJ exome

AF:

0.00196

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000443

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.0251

AC:

3824

AN:

152314

Hom.:

163

Cov.:

AF XY:

0.0241

AC XY:

1793

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0859

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00516

Hom.:

Bravo

AF:

0.0282

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0826

AC:

364

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00816

AC:

991

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.38

CADD

Benign

1.9

DANN

Benign

0.72

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

PROVEAN

Benign

1.3

REVEL

Benign

0.036

Sift

Pathogenic

0.0

Vest4

0.076

MVP

0.17

ClinPred

0.015

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over