ENST00000342392.3:n.*658A>G

Variant names:

• chr12-122208273-T-C
• rs12870
• ENST00000342392.3:n.*658A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000342392.3(DIABLO):​n.*658A>G variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (34823 hom., cov: 31)
  • Exomes 𝑓: 0.59 (210971 hom.)
• Consequence: DIABLO ENST00000342392.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.220
• Publications: 31 publications found

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]

ENSG00000256861 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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 rank	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.*885T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1
DIABLO	NM_001371333.1	c.*108A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000464942.7	NP_001358262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000256861	ENST00000535844.1	n.*622A>G		non_coding_transcript_exon_variant	Exon 16 of 16	2		ENSP00000454454.1
B3GNT4	ENST00000324189.5	c.*885T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_030765.4	ENSP00000319636.4
DIABLO	ENST00000464942.7	c.*108A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_001371333.1	ENSP00000442360.2
ENSG00000256861	ENST00000535844.1	n.*622A>G		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000454454.1

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

GnomAD2 exomes AF: 0.605 AC: 125475 AN: 207302 AF XY: 0.602

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 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

African (AFR) AF: 0.895 AC: 25164 AN: 28104

American (AMR) AF: 0.547 AC: 22590 AN: 41322

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 13851 AN: 24240

East Asian (EAS) AF: 0.767 AC: 29053 AN: 37886

South Asian (SAS) AF: 0.592 AC: 47174 AN: 79630

European-Finnish (FIN) AF: 0.509 AC: 20087 AN: 39456

Middle Eastern (MID) AF: 0.553 AC: 2041 AN: 3692

European-Non Finnish (NFE) AF: 0.578 AC: 515580 AN: 892102

Other (OTH) AF: 0.602 AC: 31250 AN: 51876

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

African (AFR) AF: 0.882 AC: 36599 AN: 41512

American (AMR) AF: 0.566 AC: 8650 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 2000 AN: 3470

East Asian (EAS) AF: 0.796 AC: 4086 AN: 5136

South Asian (SAS) AF: 0.592 AC: 2853 AN: 4822

European-Finnish (FIN) AF: 0.522 AC: 5517 AN: 10560

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38743 AN: 67926

Other (OTH) AF: 0.628 AC: 1328 AN: 2114

Alfa AF: 0.591 Hom.: 58294

Bravo AF: 0.677

Asia WGS AF: 0.670 AC: 2326 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.48
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12870; hg19: chr12-122692820;