rs200524912

Variant names:

• chr12-57626971-G-A
• rs200524912
• NM_001478.5:c.1385-10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001478.5(B4GALNT1):​c.1385-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,610,250 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (6 hom.)
• Consequence: B4GALNT1 NM_001478.5 intron
• Scores: Splicing: ADA: 0.0003593
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.192
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 12-57626971-G-A is Benign according to our data. Variant chr12-57626971-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 386003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0014 (214/152326) while in subpopulation AMR AF = 0.00274 (42/15302). AF 95% confidence interval is 0.00209. There are 1 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	NM_001478.5	MANE Select	c.1385-10C>T		intron	N/A	NP_001469.1	Q00973-1
	B4GALNT1	NM_001413967.1		c.1553-10C>T		intron	N/A	NP_001400896.1
	B4GALNT1	NM_001413968.1		c.1520-10C>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.1385-10C>T		intron	N/A	ENSP00000341562.4	Q00973-1
	B4GALNT1	ENST00000882412.1		c.1520-10C>T		intron	N/A	ENSP00000552471.1
	B4GALNT1	ENST00000954202.1		c.1385-10C>T		intron	N/A	ENSP00000624261.1

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152208 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00143 AC: 345 AN: 241660 AF XY: 0.00152

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00455

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000947

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00185 AC: 2693 AN: 1457924 Hom.: 6 Cov.: 30 AF XY: 0.00188 AC XY: 1364 AN XY: 725086

African (AFR) AF: 0.000240 AC: 8 AN: 33336

American (AMR) AF: 0.00145 AC: 64 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.00415 AC: 108 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.000512 AC: 44 AN: 85856

European-Finnish (FIN) AF: 0.00111 AC: 59 AN: 53210

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5766

European-Non Finnish (NFE) AF: 0.00207 AC: 2294 AN: 1109696

Other (OTH) AF: 0.00163 AC: 98 AN: 60262

GnomAD4 genome AF: 0.00140 AC: 214 AN: 152326 Hom.: 1 Cov.: 32 AF XY: 0.00148 AC XY: 110 AN XY: 74486

African (AFR) AF: 0.000337 AC: 14 AN: 41574

American (AMR) AF: 0.00274 AC: 42 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00190 AC: 129 AN: 68028

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00132

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.27
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

Other links and lift over

dbSNP: rs200524912; hg19: chr12-58020754;