rs10083154

Variant names:

• chr12-57627150-G-A
• rs10083154
• NM_001478.5:c.1385-189C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001478.5(B4GALNT1):​c.1385-189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,874 control chromosomes in the GnomAD database, including 11,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11168 hom., cov: 31)
• Consequence: B4GALNT1 NM_001478.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149
• Publications: 18 publications found

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), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-57627150-G-A is Benign according to our data. Variant chr12-57627150-G-A is described in ClinVar as Benign. ClinVar VariationId is 1266146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	NM_001478.5	MANE Select	c.1385-189C>T		intron	N/A	NP_001469.1	Q00973-1
	B4GALNT1	NM_001413967.1		c.1553-189C>T		intron	N/A	NP_001400896.1
	B4GALNT1	NM_001413968.1		c.1520-189C>T		intron	N/A	NP_001400897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.1385-189C>T		intron	N/A	ENSP00000341562.4	Q00973-1
	B4GALNT1	ENST00000882412.1		c.1520-189C>T		intron	N/A	ENSP00000552471.1
	B4GALNT1	ENST00000954202.1		c.1385-189C>T		intron	N/A	ENSP00000624261.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56863 AN: 151756 Hom.: 11149 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 56922 AN: 151874 Hom.: 11168 Cov.: 31 AF XY: 0.383 AC XY: 28394 AN XY: 74224

African (AFR) AF: 0.428 AC: 17712 AN: 41384

American (AMR) AF: 0.344 AC: 5251 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3468

East Asian (EAS) AF: 0.631 AC: 3243 AN: 5142

South Asian (SAS) AF: 0.573 AC: 2761 AN: 4822

European-Finnish (FIN) AF: 0.397 AC: 4180 AN: 10524

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21486 AN: 67954

Other (OTH) AF: 0.336 AC: 709 AN: 2112

Alfa AF: 0.346 Hom.: 5196

Bravo AF: 0.372

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10083154;

hg19: chr12-58020933;