rs200524912

chr12-57626971-G-A

Variant summary

Our verdict is Benign. Variant got -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 splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003593
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.192

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 386003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57626971-G-A is described in Lovd as [Likely_benign].
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALNT1	NM_001478.5	c.1385-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000341156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.1385-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001478.5	P1

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

GnomAD3 exomes AF: 0.00143 AC: 345 AN: 241660 Hom.: 2 AF XY: 0.00152 AC XY: 199 AN XY: 131022

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 SAS exome AF: 0.000599

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

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.00415

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000512

Gnomad4 FIN exome AF: 0.00111

Gnomad4 NFE exome AF: 0.00207

Gnomad4 OTH exome AF: 0.00163

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

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00132

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs200524912; hg19: chr12-58020754;