12-57626577-A-G

Position:

• chr12-57626577-A-G

Variant summary

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

The NM_001478.5(B4GALNT1):​c.*167T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 768,280 control chromosomes in the GnomAD database, including 15,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2646 hom., cov: 32)
  • Exomes 𝑓: 0.20 (12781 hom.)
• Consequence: B4GALNT1 NM_001478.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32

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=-0.38).
• BP6: Variant 12-57626577-A-G is Benign according to our data. Variant chr12-57626577-A-G is described in ClinVar as [Benign]. Clinvar id is 1242221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALNT1	NM_001478.5	c.*167T>C		3_prime_UTR_variant	11/11	ENST00000341156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.*167T>C		3_prime_UTR_variant	11/11	1	NM_001478.5	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27354 AN: 152000 Hom.: 2640 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.198 AC: 122128 AN: 616162 Hom.: 12781 Cov.: 8 AF XY: 0.194 AC XY: 62194 AN XY: 320070

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.180 AC: 27375 AN: 152118 Hom.: 2646 Cov.: 32 AF XY: 0.178 AC XY: 13235 AN XY: 74394

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.167

Alfa AF: 0.187 Hom.: 621

Bravo AF: 0.182

Asia WGS AF: 0.135 AC: 473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.77

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: rs35831868; hg19: chr12-58020360;