1-235448125-G-A

Position:

• chr1-235448125-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152490.5(B3GALNT2):​c.*2081C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 151,074 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (18 hom., cov: 28)
• Consequence: B3GALNT2 NM_152490.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.381

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-235448125-G-A is Benign according to our data. Variant chr1-235448125-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1895/151074) while in subpopulation AFR AF= 0.0175 (717/40966). AF 95% confidence interval is 0.0164. There are 18 homozygotes in gnomad4. There are 893 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALNT2	NM_152490.5	c.*2081C>T		3_prime_UTR_variant	12/12	ENST00000366600.8
TBCE	NM_003193.5	c.1400-224G>A		intron_variant		ENST00000642610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.*2081C>T		3_prime_UTR_variant	12/12	1	NM_152490.5	P1
TBCE	ENST00000642610.2	c.1400-224G>A		intron_variant			NM_003193.5	P1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1887 AN: 150964 Hom.: 18 Cov.: 28

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00815

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00940

Gnomad FIN AF: 0.00373

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0106

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

GnomAD4 genome AF: 0.0125 AC: 1895 AN: 151074 Hom.: 18 Cov.: 28 AF XY: 0.0121 AC XY: 893 AN XY: 73762

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00814

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.00962

Gnomad4 FIN AF: 0.00373

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.0116 Hom.: 1

Bravo AF: 0.0127

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148331308; hg19: chr1-235611440;