dbSNP rs11616065: B4GALNT1:p.Leu342Leu (chr12-57628241-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001478.5(B4GALNT1):c.1024C>T(p.Leu342Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00899 in 1,614,272 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 74 hom. )

Consequence

B4GALNT1
NM_001478.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.27

Publications

5 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=-0.45).

BP6

Variant 12-57628241-G-A is Benign according to our data. Variant chr12-57628241-G-A is described in ClinVar as Benign. ClinVar VariationId is 413846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.27 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00732 (1115/152392) while in subpopulation NFE AF = 0.0109 (739/68046). AF 95% confidence interval is 0.0102. There are 16 homozygotes in GnomAd4. There are 502 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

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
B4GALNT1	NM_001478.5	MANE Select	c.1024C>T	p.Leu342Leu	synonymous	Exon 9 of 11	NP_001469.1
B4GALNT1	NM_001413967.1		c.1159C>T	p.Leu387Leu	synonymous	Exon 9 of 11	NP_001400896.1
B4GALNT1	NM_001413968.1		c.1159C>T	p.Leu387Leu	synonymous	Exon 9 of 11	NP_001400897.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.1024C>T	p.Leu342Leu	synonymous	Exon 9 of 11	ENSP00000341562.4
B4GALNT1	ENST00000418555.6	TSL:2	c.859C>T	p.Leu287Leu	synonymous	Exon 8 of 10	ENSP00000401601.2
B4GALNT1	ENST00000547741.1	TSL:4	c.37C>T	p.Leu13Leu	synonymous	Exon 2 of 4	ENSP00000448577.1

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1115

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.00392

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.00762

AC:

1916

AN:

251450

AF XY:

0.00795

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00639

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00917

AC:

13401

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00917

AC XY:

6668

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

33480

American (AMR)

AF:

0.00642

AC:

287

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0137

AC:

358

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00633

AC:

546

AN:

86258

European-Finnish (FIN)

AF:

0.00198

AC:

106

AN:

53410

Middle Eastern (MID)

AF:

0.0196

AC:

113

AN:

5768

European-Non Finnish (NFE)

AF:

0.0102

AC:

11390

AN:

1112008

Other (OTH)

AF:

0.00916

AC:

553

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

852

1704

2555

3407

4259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.00732

AC:

1115

AN:

152392

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41600

American (AMR)

AF:

0.00392

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00725

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

739

AN:

68046

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00840

Hom.:

Bravo

AF:

0.00829

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

B4GALNT1: BP4, BS1, BS2

not specified

Benign:1

Mar 30, 2017

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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.9

(source)

DANN

Benign

0.90

PhyloP100

3.3

PromoterAI

0.095

Neutral

(source)

Mutation Taster

=100/0

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over