rs61649746

Variant names:

• chr12-57628146-C-T
• rs61649746
• NM_001478.5:c.1119G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001478.5(B4GALNT1):​c.1119G>A​(p.Val373Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,614,100 control chromosomes in the GnomAD database, including 160 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (79 hom.)
• Consequence: B4GALNT1 NM_001478.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.129
• Publications: 3 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), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-57628146-C-T is Benign according to our data. Variant chr12-57628146-C-T is described in ClinVar as Benign. ClinVar VariationId is 239025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 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.1119G>A	p.Val373Val	synonymous	Exon 9 of 11	NP_001469.1	Q00973-1
	B4GALNT1	NM_001413967.1		c.1254G>A	p.Val418Val	synonymous	Exon 9 of 11	NP_001400896.1
	B4GALNT1	NM_001413968.1		c.1254G>A	p.Val418Val	synonymous	Exon 9 of 11	NP_001400897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.1119G>A	p.Val373Val	synonymous	Exon 9 of 11	ENSP00000341562.4	Q00973-1
	B4GALNT1	ENST00000882412.1		c.1254G>A	p.Val418Val	synonymous	Exon 9 of 11	ENSP00000552471.1
	B4GALNT1	ENST00000954202.1		c.1119G>A	p.Val373Val	synonymous	Exon 8 of 10	ENSP00000624261.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2734 AN: 152268 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00467 AC: 1173 AN: 251032 AF XY: 0.00347

Gnomad AFR exome AF: 0.0641

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00175 AC: 2552 AN: 1461714 Hom.: 79 Cov.: 32 AF XY: 0.00152 AC XY: 1107 AN XY: 727182

African (AFR) AF: 0.0632 AC: 2115 AN: 33480

American (AMR) AF: 0.00315 AC: 141 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111996

Other (OTH) AF: 0.00351 AC: 212 AN: 60394

GnomAD4 genome AF: 0.0180 AC: 2737 AN: 152386 Hom.: 81 Cov.: 33 AF XY: 0.0176 AC XY: 1310 AN XY: 74528

African (AFR) AF: 0.0618 AC: 2572 AN: 41592

American (AMR) AF: 0.00836 AC: 128 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0107 Hom.: 23

Bravo AF: 0.0206

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	B4GALNT1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs61649746; hg19: chr12-58021929;