12-57626742-C-T

Variant names:

• chr12-57626742-C-T
• rs141524511
• NM_001478.5:c.*2G>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.*2G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,614,070 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (28 hom.)
• Consequence: B4GALNT1 NM_001478.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0810

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=-0.81).
• BP6: Variant 12-57626742-C-T is Benign according to our data. Variant chr12-57626742-C-T is described in ClinVar as [Benign]. Clinvar id is 387791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1608/152328) while in subpopulation AFR AF= 0.0365 (1515/41560). AF 95% confidence interval is 0.0349. There are 32 homozygotes in gnomad4. There are 758 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT1	NM_001478.5	c.*2G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341156.9	NP_001469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156	c.*2G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001478.5	ENSP00000341562.4

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1600 AN: 152210 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00296 AC: 745 AN: 251384 Hom.: 13 AF XY: 0.00239 AC XY: 324 AN XY: 135846

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00124 AC: 1807 AN: 1461742 Hom.: 28 Cov.: 31 AF XY: 0.00110 AC XY: 802 AN XY: 727170

Gnomad4 AFR exome AF: 0.0375

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0106 AC: 1608 AN: 152328 Hom.: 32 Cov.: 32 AF XY: 0.0102 AC XY: 758 AN XY: 74502

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.00444

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00570 Hom.: 6

Bravo AF: 0.0125

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 18, 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

- -

B4GALNT1-related disorder Benign:1

May 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs141524511; hg19: chr12-58020525;