rs291396

Variant names:

• chr1-235489208-C-T
• rs291396
• NM_152490.5:c.321G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-235489208-C-T
• chr1-235489208-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4 BP6_Moderate BP7 BA1

The NM_152490.5(B3GALNT2):​c.321G>A​(p.Glu107Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,652 control chromosomes in the GnomAD database, including 184,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16000 hom., cov: 32)
  • Exomes 𝑓: 0.47 (168357 hom.)
• Consequence: B3GALNT2 NM_152490.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.249
• Publications: 26 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• 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=-0.09).
• BP6: Variant 1-235489208-C-T is Benign according to our data. Variant chr1-235489208-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 473884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.249 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152490.5. 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
	B3GALNT2	NM_152490.5	MANE Select	c.321G>A	p.Glu107Glu	synonymous	Exon 3 of 12	NP_689703.1	Q8NCR0-1
	B3GALNT2	NM_001277155.3		c.444G>A	p.Glu148Glu	synonymous	Exon 4 of 8	NP_001264084.1	Q8NCR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.321G>A	p.Glu107Glu	synonymous	Exon 3 of 12	ENSP00000355559.3	Q8NCR0-1
	B3GALNT2	ENST00000313984.3	TSL:1	c.444G>A	p.Glu148Glu	synonymous	Exon 4 of 8	ENSP00000315678.3	Q8NCR0-2
	B3GALNT2	ENST00000954792.1		c.444G>A	p.Glu148Glu	synonymous	Exon 4 of 13	ENSP00000624851.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68251 AN: 151900 Hom.: 15986 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.471 AC: 688384 AN: 1461632 Hom.: 168357 Cov.: 62 AF XY: 0.467 AC XY: 339453 AN XY: 727102

African (AFR) AF: 0.428 AC: 14315 AN: 33478

American (AMR) AF: 0.255 AC: 11414 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 12797 AN: 26130

East Asian (EAS) AF: 0.131 AC: 5207 AN: 39692

South Asian (SAS) AF: 0.280 AC: 24178 AN: 86230

European-Finnish (FIN) AF: 0.524 AC: 27946 AN: 53342

Middle Eastern (MID) AF: 0.465 AC: 2683 AN: 5764

European-Non Finnish (NFE) AF: 0.506 AC: 562679 AN: 1111892

Other (OTH) AF: 0.450 AC: 27165 AN: 60388

GnomAD4 genome AF: 0.449 AC: 68292 AN: 152020 Hom.: 16000 Cov.: 32 AF XY: 0.442 AC XY: 32852 AN XY: 74282

African (AFR) AF: 0.431 AC: 17884 AN: 41470

American (AMR) AF: 0.355 AC: 5420 AN: 15272

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

East Asian (EAS) AF: 0.144 AC: 745 AN: 5174

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4816

European-Finnish (FIN) AF: 0.522 AC: 5499 AN: 10536

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

European-Non Finnish (NFE) AF: 0.504 AC: 34247 AN: 67958

Other (OTH) AF: 0.480 AC: 1015 AN: 2116

Alfa AF: 0.482 Hom.: 28473

Bravo AF: 0.436

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.090
CADD	Benign	5.1
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs291396; hg19: chr1-235652513;