rs715930

Variant names:

• chr12-57630198-C-A
• rs715930
• NM_001478.5:c.666G>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001413981.1(B4GALNT1):​c.-322G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,614,046 control chromosomes in the GnomAD database, including 37,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3977 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33825 hom.)
• Consequence: B4GALNT1 NM_001413981.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.63

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 12-57630198-C-A is Benign according to our data. Variant chr12-57630198-C-A is described in ClinVar as [Benign]. Clinvar id is 380770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5	c.666G>T	p.Leu222Leu	synonymous_variant	Exon 6 of 11	ENST00000341156.9	NP_001469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.666G>T	p.Leu222Leu	synonymous_variant	Exon 6 of 11	1	NM_001478.5	ENSP00000341562.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33923 AN: 152064 Hom.: 3971 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.213 AC: 53492 AN: 251354 Hom.: 6179 AF XY: 0.203 AC XY: 27546 AN XY: 135856

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.331

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.211 AC: 308489 AN: 1461864 Hom.: 33825 Cov.: 35 AF XY: 0.207 AC XY: 150469 AN XY: 727232

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.223 AC: 33964 AN: 152182 Hom.: 3977 Cov.: 33 AF XY: 0.220 AC XY: 16359 AN XY: 74414

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.198

Alfa AF: 0.205 Hom.: 5655

Bravo AF: 0.232

Asia WGS AF: 0.145 AC: 507 AN: 3478

EpiCase AF: 0.198

EpiControl AF: 0.191

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Feb 08, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	11
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs715930; hg19: chr12-58023981; COSMIC: COSV57542001; COSMIC: COSV57542001;