rs4846914

Variant names:

• chr1-230159944-G-A
• rs4846914
• NM_004481.5:c.127-18274G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004481.5(GALNT2):​c.127-18274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,022 control chromosomes in the GnomAD database, including 18,286 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (18286 hom., cov: 31)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683
• Publications: 168 publications found

Genes affected

GALNT2 (HGNC:4124): (polypeptide N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GALNT2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type iit

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004481.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	NM_004481.5	MANE Select	c.127-18274G>A		intron	N/A	NP_004472.1	A0A1L7NY50
	GALNT2	NM_001291866.2		c.13-18274G>A		intron	N/A	NP_001278795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	ENST00000366672.5	TSL:1 MANE Select	c.127-18274G>A		intron	N/A	ENSP00000355632.4	Q10471-1
	GALNT2	ENST00000935982.1		c.127-18274G>A		intron	N/A	ENSP00000606041.1
	GALNT2	ENST00000950855.1		c.127-18274G>A		intron	N/A	ENSP00000620914.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68019 AN: 151902 Hom.: 18279 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.448 AC: 68034 AN: 152022 Hom.: 18286 Cov.: 31 AF XY: 0.444 AC XY: 33021 AN XY: 74296

African (AFR) AF: 0.138 AC: 5716 AN: 41488

American (AMR) AF: 0.554 AC: 8463 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1190 AN: 5158

South Asian (SAS) AF: 0.421 AC: 2022 AN: 4806

European-Finnish (FIN) AF: 0.539 AC: 5705 AN: 10576

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41040 AN: 67938

Other (OTH) AF: 0.505 AC: 1066 AN: 2110

Alfa AF: 0.550 Hom.: 92869

Bravo AF: 0.436

Asia WGS AF: 0.334 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs4846914; hg19: chr1-230295691;