12-122208273-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030765.4(B3GNT4):c.*885T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,350,324 control chromosomes in the GnomAD database, including 245,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (34823 hom., cov: 31)
  • Exomes 𝑓: 0.59 (210971 hom.)
• Consequence: B3GNT4 NM_030765.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.220

Genes affected

DIABLO (HGNC:21528): (diablo IAP-binding mitochondrial protein) This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of nonsyndromic deafness-64. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

B3GNT4 (HGNC:15683): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase protein family. The encoded enzyme is involved in the biosynthesis of poly-N-acetyllactosamine chains and prefers lacto-N-neotetraose as a substrate. It is a type II transmembrane protein. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-122208273-T-C is Benign according to our data. Variant chr12-122208273-T-C is described in ClinVar as [Benign]. Clinvar id is 1247587.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIABLO	NM_001371333.1	c.*108A>G		3_prime_UTR_variant	6/6	ENST00000464942.7
B3GNT4	NM_030765.4	c.*885T>C		3_prime_UTR_variant	3/3	ENST00000324189.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GNT4	ENST00000324189.5	c.*885T>C		3_prime_UTR_variant	3/3	1	NM_030765.4	A2
DIABLO	ENST00000464942.7	c.*108A>G		3_prime_UTR_variant	6/6	1	NM_001371333.1	P1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100217 AN: 151898 Hom.: 34782 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.629

GnomAD3 exomes AF: 0.605 AC: 125475 AN: 207302 Hom.: 38819 AF XY: 0.602 AC XY: 68251 AN XY: 113462

Gnomad AFR exome AF: 0.890

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.797

Gnomad SAS exome AF: 0.593

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.590 AC: 706790 AN: 1198308 Hom.: 210971 Cov.: 17 AF XY: 0.588 AC XY: 356487 AN XY: 605958

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.602

GnomAD4 genome AF: 0.660 AC: 100319 AN: 152016 Hom.: 34823 Cov.: 31 AF XY: 0.655 AC XY: 48696 AN XY: 74296

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.628

Alfa AF: 0.578 Hom.: 37363

Bravo AF: 0.677

Asia WGS AF: 0.670 AC: 2326 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.1
Dann	Benign	0.48

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: rs12870; hg19: chr12-122692820;