chr12-122208273-T-C

Variant names:

• chr12-122208273-T-C
• rs12870
• NM_030765.4:c.*885T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.220
• Publications: 31 publications found

Genes affected

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]

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]

DIABLO Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant nonsyndromic hearing loss 64

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000256861 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1247587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030765.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT4	NM_030765.4	MANE Select	c.*885T>C		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
	DIABLO	NM_001371333.1	MANE Select	c.*108A>G		3_prime_UTR	Exon 6 of 6	NP_001358262.1	A0A0S2Z5U7
	B3GNT4	NM_001330492.2		c.*885T>C		3_prime_UTR	Exon 2 of 2	NP_001317421.1	Q9C0J1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*885T>C		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1
	DIABLO	ENST00000464942.7	TSL:1 MANE Select	c.*108A>G		3_prime_UTR	Exon 6 of 6	ENSP00000442360.2	Q9NR28-1
	DIABLO	ENST00000267169.11	TSL:1	c.*284A>G		3_prime_UTR	Exon 7 of 7	ENSP00000267169.7	A0A2U3TZH2

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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;