rs149670131

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001478.5(B4GALNT1):c.728A>G(p.Glu243Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000484 in 1,595,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E243K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

B4GALNT1
NM_001478.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.20

Publications

2 publications found

Variant links:

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

B4GALNT1 Gene-Disease associations (from GenCC):

complex hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 26
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

B4GALNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01669401).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000571 (87/152254) while in subpopulation SAS AF = 0.00187 (9/4816). AF 95% confidence interval is 0.000975. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001478.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT1	NM_001478.5	MANE Select	c.728A>G	p.Glu243Gly	missense	Exon 7 of 11	NP_001469.1	Q00973-1
B4GALNT1	NM_001413967.1		c.728A>G	p.Glu243Gly	missense	Exon 7 of 11	NP_001400896.1
B4GALNT1	NM_001413968.1		c.728A>G	p.Glu243Gly	missense	Exon 7 of 11	NP_001400897.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.728A>G	p.Glu243Gly	missense	Exon 7 of 11	ENSP00000341562.4	Q00973-1
B4GALNT1	ENST00000882412.1		c.728A>G	p.Glu243Gly	missense	Exon 7 of 11	ENSP00000552471.1
B4GALNT1	ENST00000954202.1		c.728A>G	p.Glu243Gly	missense	Exon 6 of 10	ENSP00000624261.1

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000619

AC:

151

AN:

244068

AF XY:

0.000645

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00147

Gnomad EAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.000859

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000475

AC:

685

AN:

1442862

Hom.:

Cov.:

AF XY:

0.000489

AC XY:

349

AN XY:

714268

show subpopulations

African (AFR)

AF:

0.0000908

AC:

AN:

33054

American (AMR)

AF:

0.000207

AC:

AN:

43436

Ashkenazi Jewish (ASJ)

AF:

0.000899

AC:

AN:

25594

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39266

South Asian (SAS)

AF:

0.00155

AC:

131

AN:

84740

European-Finnish (FIN)

AF:

0.000245

AC:

AN:

53152

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.000418

AC:

459

AN:

1098398

Other (OTH)

AF:

0.000638

AC:

AN:

59516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000571

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41552

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00187

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000926

AC:

AN:

68000

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000661

Hom.:

Bravo

AF:

0.000442

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000824

AC:

100

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 26 (1)

not provided (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

M_CAP

Benign

0.0067

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.93

PhyloP100

4.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.0

REVEL

Benign

0.056

Sift

Benign

0.27

Sift4G

Benign

0.40

Polyphen

0.0010

Vest4

0.22

MVP

0.31

MPC

0.23

ClinPred

0.019

GERP RS

2.8

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.11

gMVP

0.76

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over