rs12870

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-122208273-T-A
• chr12-122208273-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000342392.3(DIABLO):​n.*658A>T 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 0.00000222 in 1,352,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: DIABLO ENST00000342392.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342392.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT4	NM_030765.4	MANE Select	c.*885T>A		3_prime_UTR	Exon 3 of 3	NP_110392.1
	DIABLO	NM_001371333.1	MANE Select	c.*108A>T		3_prime_UTR	Exon 6 of 6	NP_001358262.1
	B3GNT4	NM_001330492.2		c.*885T>A		3_prime_UTR	Exon 2 of 2	NP_001317421.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIABLO	ENST00000342392.3	TSL:1	n.*658A>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000339963.3
	ENSG00000256861	ENST00000535844.1	TSL:2	n.*622A>T		non_coding_transcript_exon	Exon 16 of 16	ENSP00000454454.1
	B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*885T>A		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151958 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000482 AC: 1 AN: 207302 AF XY: 0.00

Gnomad AFR exome AF: 0.0000782

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.33e-7 AC: 1 AN: 1200450 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 606962

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000356 AC: 1 AN: 28120

American (AMR) AF: 0.00 AC: 0 AN: 41364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24266

East Asian (EAS) AF: 0.00 AC: 0 AN: 37910

South Asian (SAS) AF: 0.00 AC: 0 AN: 79700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 893970

Other (OTH) AF: 0.00 AC: 0 AN: 51946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151958 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74210

African (AFR) AF: 0.0000483 AC: 2 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67954

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 58294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.66
PhyloP100		0.22

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;