Variant rs78105569 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001478.5(B4GALNT1):c.812-7A>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008580

Clinical Significance

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

Conservation

PhyloP100: 1.59

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALNT1	NM_001478.5 linkuse as main transcript	c.812-7A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000341156.9	NP_001469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9 linkuse as main transcript	c.812-7A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001478.5	ENSP00000341562	P1	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

GnomAD3 exomes

AF:

0.00197

AC:

494

AN:

251380

Hom.:

AF XY:

0.00148

AC XY:

201

AN XY:

135862

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 SAS 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

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00645

AC:

981

AN:

152104

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

433

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.00452

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00616

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2020	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over