rs810205

Positions:

• chr12-57630495-C-G
• chr12-57630495-C-T

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.514G>C​(p.Gly172Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,609,128 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (84 hom., cov: 33)
  • Exomes 𝑓: 0.018 (313 hom.)
• Consequence: B4GALNT1 NM_001478.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.526

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021012425).
• BP6: Variant 12-57630495-C-G is Benign according to our data. Variant chr12-57630495-C-G is described in ClinVar as [Benign]. Clinvar id is 380791.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 = 0.0279 (4244/152302) while in subpopulation AFR AF= 0.0485 (2014/41554). AF 95% confidence interval is 0.0467. There are 84 homozygotes in gnomad4. There are 2156 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALNT1	NM_001478.5	c.514G>C	p.Gly172Arg	missense_variant	5/11	ENST00000341156.9	NP_001469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.514G>C	p.Gly172Arg	missense_variant	5/11	1	NM_001478.5	ENSP00000341562.4

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4241 AN: 152184 Hom.: 83 Cov.: 33

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0191 AC: 4719 AN: 246592 Hom.: 71 AF XY: 0.0188 AC XY: 2505 AN XY: 133156

Gnomad AFR exome AF: 0.0461

Gnomad AMR exome AF: 0.00637

Gnomad ASJ exome AF: 0.0247

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0196

Gnomad FIN exome AF: 0.0461

Gnomad NFE exome AF: 0.0165

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0183 AC: 26593 AN: 1456826 Hom.: 313 Cov.: 32 AF XY: 0.0182 AC XY: 13168 AN XY: 724394

Gnomad4 AFR exome AF: 0.0490

Gnomad4 AMR exome AF: 0.00751

Gnomad4 ASJ exome AF: 0.0234

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.0445

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0279 AC: 4244 AN: 152302 Hom.: 84 Cov.: 33 AF XY: 0.0290 AC XY: 2156 AN XY: 74466

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0170 Hom.: 23

Bravo AF: 0.0253

TwinsUK AF: 0.0143 AC: 53

ALSPAC AF: 0.0132 AC: 51

ESP6500AA AF: 0.0497 AC: 219

ESP6500EA AF: 0.0180 AC: 155

ExAC AF: 0.0198 AC: 2399

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2016

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. -

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.20	T;.;T;.;.;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.86	D;D;D;.;D;D
MetaRNN	Benign	0.0021	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.;L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.50	N;N;.;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.12	T;T;.;T;T;T
Sift4G	Benign	0.58	T;T;T;T;T;.
Polyphen		0.0	B;.;P;.;.;.
Vest4		0.22
MPC		0.31
ClinPred		0.014	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs810205; hg19: chr12-58024278;