12-122208327-A-G

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.*939A>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 0.0413 in 1,597,692 control chromosomes in the GnomAD database, including 12,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (6226 hom., cov: 32)
  • Exomes 𝑓: 0.028 (5958 hom.)
• Consequence: B3GNT4 NM_030765.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.71

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=-0.91).
• BP6: Variant 12-122208327-A-G is Benign according to our data. Variant chr12-122208327-A-G is described in ClinVar as [Benign]. Clinvar id is 1249498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIABLO	NM_001371333.1	c.*54T>C		3_prime_UTR_variant	6/6	ENST00000464942.7
B3GNT4	NM_030765.4	c.*939A>G		3_prime_UTR_variant	3/3	ENST00000324189.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GNT4	ENST00000324189.5	c.*939A>G		3_prime_UTR_variant	3/3	1	NM_030765.4	A2
DIABLO	ENST00000464942.7	c.*54T>C		3_prime_UTR_variant	6/6	1	NM_001371333.1	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25007 AN: 152070 Hom.: 6207 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.0586 AC: 14358 AN: 244920 Hom.: 2528 AF XY: 0.0503 AC XY: 6693 AN XY: 132980

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.0315

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.0472

Gnomad SAS exome AF: 0.0620

Gnomad FIN exome AF: 0.00414

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0357

GnomAD4 exome AF: 0.0283 AC: 40846 AN: 1445504 Hom.: 5958 Cov.: 29 AF XY: 0.0276 AC XY: 19886 AN XY: 719928

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.0351

Gnomad4 ASJ exome AF: 0.0415

Gnomad4 EAS exome AF: 0.0375

Gnomad4 SAS exome AF: 0.0613

Gnomad4 FIN exome AF: 0.00411

Gnomad4 NFE exome AF: 0.00826

Gnomad4 OTH exome AF: 0.0529

GnomAD4 genome AF: 0.165 AC: 25068 AN: 152188 Hom.: 6226 Cov.: 32 AF XY: 0.160 AC XY: 11924 AN XY: 74414

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0512 Hom.: 991

Bravo AF: 0.186

Asia WGS AF: 0.0910 AC: 315 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 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.028
Dann	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7294427; hg19: chr12-122692874;