1-235448206-A-C

Position:

• chr1-235448206-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152490.5(B3GALNT2):​c.*2000T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 716,800 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (31 hom., cov: 26)
  • Exomes 𝑓: 0.013 (77 hom.)
• Consequence: B3GALNT2 NM_152490.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0610

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]

TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-235448206-A-C is Benign according to our data. Variant chr1-235448206-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1186898.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 = 0.0191 (2801/146588) while in subpopulation AFR AF= 0.0349 (1326/38010). AF 95% confidence interval is 0.0333. There are 31 homozygotes in gnomad4. There are 1319 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALNT2	NM_152490.5	c.*2000T>G		3_prime_UTR_variant	12/12	ENST00000366600.8
TBCE	NM_003193.5	c.1400-143A>C		intron_variant		ENST00000642610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.*2000T>G		3_prime_UTR_variant	12/12	1	NM_152490.5	P1
TBCE	ENST00000642610.2	c.1400-143A>C		intron_variant			NM_003193.5	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2788 AN: 146486 Hom.: 29 Cov.: 26

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00814

Gnomad FIN AF: 0.00290

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0161

GnomAD4 exome AF: 0.0129 AC: 7364 AN: 570212 Hom.: 77 AF XY: 0.0128 AC XY: 3940 AN XY: 307024

Gnomad4 AFR exome AF: 0.0348

Gnomad4 AMR exome AF: 0.00867

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00957

Gnomad4 FIN exome AF: 0.00453

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0191 AC: 2801 AN: 146588 Hom.: 31 Cov.: 26 AF XY: 0.0185 AC XY: 1319 AN XY: 71434

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00836

Gnomad4 FIN AF: 0.00290

Gnomad4 NFE AF: 0.0157

Gnomad4 OTH AF: 0.0159

Alfa AF: 0.0165 Hom.: 1

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 06, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs112398616; hg19: chr1-235611521;