rs78105569

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001478.5(B4GALNT1):c.812-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,613,962 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 6 hom. )

Consequence

B4GALNT1
NM_001478.5 splice_region, intron

Scores

Splicing: ADA: 0.00008580

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.59

Publications

0 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-57628910-T-A is Benign according to our data. Variant chr12-57628910-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 413845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00645 (981/152104) while in subpopulation AFR AF = 0.0213 (882/41492). AF 95% confidence interval is 0.0201. There are 13 homozygotes in GnomAd4. There are 433 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5 link	c.812-7A>T		splice_region_variant, intron_variant	Intron 7 of 10	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.812-7A>T		splice_region_variant, intron_variant	Intron 7 of 10	1	NM_001478.5	ENSP00000341562.4		Q00973-1

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

980

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00622

GnomAD2 exomes

AF:

0.00197

AC:

494

AN:

251380

AF XY:

0.00148

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000726

AC:

1061

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000649

AC XY:

472

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0198

AC:

662

AN:

33480

American (AMR)

AF:

0.00266

AC:

119

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000156

AC:

174

AN:

1111992

Other (OTH)

AF:

0.00151

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00645

AC:

981

AN:

152104

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

433

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0213

AC:

882

AN:

41492

American (AMR)

AF:

0.00452

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

67964

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000470

Hom.:

Bravo

AF:

0.00753

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 28, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic paraplegia

Benign:1

Feb 03, 2025

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_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

1.6

PromoterAI

0.0033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000086

dbscSNV1_RF

Benign

0.052

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over