12-122208327-A-G

Variant names:

• chr12-122208327-A-G
• rs7294427
• NM_030765.4:c.*939A>G

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.71

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]

ENSG00000256861 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.*939A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1
DIABLO	NM_001371333.1	c.*54T>C		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
B3GNT4	ENST00000324189.5	c.*939A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_030765.4	ENSP00000319636.4
DIABLO	ENST00000464942	c.*54T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_001371333.1	ENSP00000442360.2
ENSG00000256861	ENST00000535844.1	n.*568T>C		non_coding_transcript_exon_variant	Exon 16 of 16	2		ENSP00000454454.1
ENSG00000256861	ENST00000535844.1	n.*568T>C		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000454454.1

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

GnomAD2 exomes AF: 0.0586 AC: 14358 AN: 244920 AF XY: 0.0503

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 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 AC: 18776 AN: 33190

Gnomad4 AMR exome AF: 0.0351 AC: 1571 AN: 44702

Gnomad4 ASJ exome AF: 0.0415 AC: 1082 AN: 26080

Gnomad4 EAS exome AF: 0.0375 AC: 1488 AN: 39642

Gnomad4 SAS exome AF: 0.0613 AC: 5267 AN: 85984

Gnomad4 FIN exome AF: 0.00411 AC: 199 AN: 48398

Gnomad4 NFE exome AF: 0.00826 AC: 9114 AN: 1103494

Gnomad4 Remaining exome AF: 0.0529 AC: 3165 AN: 59872

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 AC: 0.538374 AN: 0.538374

Gnomad4 AMR AF: 0.0654 AC: 0.0653509 AN: 0.0653509

Gnomad4 ASJ AF: 0.0421 AC: 0.0420507 AN: 0.0420507

Gnomad4 EAS AF: 0.0487 AC: 0.0487051 AN: 0.0487051

Gnomad4 SAS AF: 0.0717 AC: 0.0717247 AN: 0.0717247

Gnomad4 FIN AF: 0.00452 AC: 0.00451892 AN: 0.00451892

Gnomad4 NFE AF: 0.0102 AC: 0.0101741 AN: 0.0101741

Gnomad4 OTH AF: 0.115 AC: 0.115057 AN: 0.115057

Alfa AF: 0.0572 Hom.: 1244

Bravo AF: 0.186

Asia WGS AF: 0.0910 AC: 315 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 16, 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	-0.91
CADD	Benign	0.028
DANN	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Publications

LitVar

Other links and lift over

dbSNP: rs7294427; hg19: chr12-122692874;