rs715930

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001478.5(B4GALNT1):c.666G>T(p.Leu222Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,614,046 control chromosomes in the GnomAD database, including 37,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L222L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.22 ( 3977 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33825 hom. )

Consequence

B4GALNT1
NM_001478.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.63

Publications

38 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

B4GALNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 12-57630198-C-A is Benign according to our data. Variant chr12-57630198-C-A is described in ClinVar as Benign. ClinVar VariationId is 380770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5 link	c.666G>T	p.Leu222Leu	synonymous_variant	Exon 6 of 11	ENST00000341156.9	NP_001469.1	Q00973-1B4DSP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9 link	c.666G>T	p.Leu222Leu	synonymous_variant	Exon 6 of 11	1	NM_001478.5	ENSP00000341562.4		Q00973-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33923

AN:

152064

Hom.:

3971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.195

GnomAD2 exomes

AF:

0.213

AC:

53492

AN:

251354

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.211

AC:

308489

AN:

1461864

Hom.:

33825

Cov.:

AF XY:

0.207

AC XY:

150469

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.279

AC:

9351

AN:

33480

American (AMR)

AF:

0.324

AC:

14505

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3229

AN:

26136

East Asian (EAS)

AF:

0.114

AC:

4512

AN:

39700

South Asian (SAS)

AF:

0.143

AC:

12305

AN:

86254

European-Finnish (FIN)

AF:

0.207

AC:

11033

AN:

53420

Middle Eastern (MID)

AF:

0.108

AC:

622

AN:

5768

European-Non Finnish (NFE)

AF:

0.217

AC:

241033

AN:

1111994

Other (OTH)

AF:

0.197

AC:

11899

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

17740

35480

53221

70961

88701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8444

16888

25332

33776

42220

<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:

0.223

AC:

33964

AN:

152182

Hom.:

3977

Cov.:

AF XY:

0.220

AC XY:

16359

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.269

AC:

11165

AN:

41506

American (AMR)

AF:

0.267

AC:

4080

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

390

AN:

3472

East Asian (EAS)

AF:

0.130

AC:

671

AN:

5172

South Asian (SAS)

AF:

0.153

AC:

739

AN:

4826

European-Finnish (FIN)

AF:

0.201

AC:

2130

AN:

10602

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14198

AN:

68002

Other (OTH)

AF:

0.198

AC:

417

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1381

2761

4142

5522

6903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.209

Hom.:

7021

Bravo

AF:

0.232

Asia WGS

AF:

0.145

AC:

507

AN:

3478

EpiCase

AF:

0.198

EpiControl

AF:

0.191

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 08, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Spastic paraplegia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.6

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over