11-369948-G-C

Variant names:

• chr11-369948-G-C
• rs892200851
• NM_178537.5:c.145G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_178537.5(B4GALNT4):​c.145G>C​(p.Gly49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 976,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G49E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000070 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: B4GALNT4 NM_178537.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.916
• Publications: 0 publications found

Genes affected

B4GALNT4 (HGNC:26315): (beta-1,4-N-acetyl-galactosaminyltransferase 4) Enables acetylgalactosaminyltransferase activity. Predicted to be located in Golgi cisterna membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19123596).
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5	c.145G>C	p.Gly49Arg	missense_variant	Exon 1 of 20	ENST00000329962.11	NP_848632.2
B4GALNT4	XR_001747858.2	n.450G>C		non_coding_transcript_exon_variant	Exon 1 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT4	ENST00000329962.11	c.145G>C	p.Gly49Arg	missense_variant	Exon 1 of 20	1	NM_178537.5	ENSP00000328277.6
B4GALNT4	ENST00000530717.1	n.153G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0000702 AC: 10 AN: 142506 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00209

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 302 AF XY: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000720 AC: 6 AN: 833710 Hom.: 0 Cov.: 23 AF XY: 0.0000104 AC XY: 4 AN XY: 385116

African (AFR) AF: 0.00 AC: 0 AN: 15778

American (AMR) AF: 0.00 AC: 0 AN: 1012

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 2 AN: 5166

East Asian (EAS) AF: 0.00 AC: 0 AN: 3740

South Asian (SAS) AF: 0.0000578 AC: 1 AN: 17300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1644

European-Non Finnish (NFE) AF: 0.00000394 AC: 3 AN: 761416

Other (OTH) AF: 0.00 AC: 0 AN: 27310

GnomAD4 genome AF: 0.0000702 AC: 10 AN: 142506 Hom.: 0 Cov.: 25 AF XY: 0.0000433 AC XY: 3 AN XY: 69220

African (AFR) AF: 0.0000253 AC: 1 AN: 39500

American (AMR) AF: 0.00 AC: 0 AN: 14482

Ashkenazi Jewish (ASJ) AF: 0.00209 AC: 7 AN: 3356

East Asian (EAS) AF: 0.00 AC: 0 AN: 4884

South Asian (SAS) AF: 0.00 AC: 0 AN: 4624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000309 AC: 2 AN: 64658

Other (OTH) AF: 0.00 AC: 0 AN: 1962

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.145G>C (p.G49R) alteration is located in exon 1 (coding exon 1) of the B4GALNT4 gene. This alteration results from a G to C substitution at nucleotide position 145, causing the glycine (G) at amino acid position 49 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.92
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.10
Sift	Benign	0.12	T
Sift4G	Benign	0.37	T
Polyphen		0.99	D
Vest4		0.21
MutPred		0.42		Gain of solvent accessibility (P = 0.0171);
MVP		0.082
MPC		1.0
ClinPred		0.74	D
GERP RS		1.0
PromoterAI		-0.023	Neutral
Varity_R		0.25
gMVP		0.43
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs892200851; hg19: chr11-369948;