1-235498234-G-A

Variant names:

• chr1-235498234-G-A
• rs696244
• NM_152490.5:c.113-3406C>T

Variant summary

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

The NM_152490.5(B3GALNT2):​c.113-3406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,894 control chromosomes in the GnomAD database, including 16,182 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 (16182 hom., cov: 31)
• Consequence: B3GALNT2 NM_152490.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• Publications: 11 publications found

Genes affected

B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]

B3GALNT2 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.113-3406C>T		intron_variant	Intron 1 of 11	ENST00000366600.8	NP_689703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.113-3406C>T		intron_variant	Intron 1 of 11	1	NM_152490.5	ENSP00000355559.3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68698 AN: 151776 Hom.: 16169 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.453 AC: 68737 AN: 151894 Hom.: 16182 Cov.: 31 AF XY: 0.445 AC XY: 33055 AN XY: 74222

African (AFR) AF: 0.443 AC: 18335 AN: 41392

American (AMR) AF: 0.355 AC: 5422 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1670 AN: 3472

East Asian (EAS) AF: 0.145 AC: 749 AN: 5174

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4822

European-Finnish (FIN) AF: 0.523 AC: 5505 AN: 10530

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34236 AN: 67932

Other (OTH) AF: 0.479 AC: 1009 AN: 2106

Alfa AF: 0.478 Hom.: 23609

Bravo AF: 0.440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
PhyloP100		-0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs696244; hg19: chr1-235661544;