rs201892419

chr11-66347191-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP6 BS1

The NM_006876.3(B4GAT1):c.355C>A(p.Pro119Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000613 in 1,583,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: B4GAT1 NM_006876.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 7.16

Genes affected

B4GAT1 (HGNC:15685): (beta-1,4-glucuronyltransferase 1) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein. It is essential for the synthesis of poly-N-acetyllactosamine, a determinant for the blood group i antigen. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04965064).
• BP6: Variant 11-66347191-G-T is Benign according to our data. Variant chr11-66347191-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 581531.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000788 (12/152334) while in subpopulation EAS AF= 0.00193 (10/5168). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GAT1	NM_006876.3	c.355C>A	p.Pro119Thr	missense_variant	1/2	ENST00000311181.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GAT1	ENST00000311181.5	c.355C>A	p.Pro119Thr	missense_variant	1/2	1	NM_006876.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000182 AC: 35 AN: 192766 Hom.: 0 AF XY: 0.000201 AC XY: 21 AN XY: 104494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00249

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000594 AC: 85 AN: 1430744 Hom.: 0 Cov.: 31 AF XY: 0.0000423 AC XY: 30 AN XY: 709454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000252

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00109

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.000693

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74494

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000334 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.000167 AC: 20

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 08, 2019

The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in heterozygous state in an individual with isolated hypogonadotropic hypogonadism (Zhou et al., 2018); This variant is associated with the following publications: (PMID: 30098700) -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Uncertain	0.12
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.68	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.73
MVP		0.20
MPC		2.1
ClinPred		0.25	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.93

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: rs201892419; hg19: chr11-66114662;