Variant 12-14840920-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021071.4(ART4):c.378T>C(p.Tyr126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,614,000 control chromosomes in the GnomAD database, including 103,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 8334 hom., cov: 32)

Exomes 𝑓: 0.35 ( 95042 hom. )

Consequence

ART4
NM_021071.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0410

Variant links:

Genes affected

ART4 (HGNC:726): (ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)) This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known. [provided by RefSeq, Jul 2008]

ART4 links:

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

C12orf60 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-14840920-A-G is Benign according to our data. Variant chr12-14840920-A-G is described in ClinVar as [Benign]. Clinvar id is 3060314.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.041 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ART4	NM_021071.4 linkuse as main transcript	c.378T>C	p.Tyr126=	synonymous_variant	2/3	ENST00000228936.6	NP_066549.2
ART4	NM_001354646.2 linkuse as main transcript	c.378T>C	p.Tyr126=	synonymous_variant	2/2		NP_001341575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ART4	ENST00000228936.6 linkuse as main transcript	c.378T>C	p.Tyr126=	synonymous_variant	2/3	1	NM_021071.4	ENSP00000228936	P1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48784

AN:

152010

Hom.:

8322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.0881

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.317

AC:

79720

AN:

251178

Hom.:

13507

AF XY:

0.321

AC XY:

43592

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.0849

Gnomad SAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.355

AC:

518609

AN:

1461872

Hom.:

95042

Cov.:

AF XY:

0.353

AC XY:

256863

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.0894

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.321

AC:

48816

AN:

152128

Hom.:

8334

Cov.:

AF XY:

0.315

AC XY:

23446

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.0880

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.354

Hom.:

10279

Bravo

AF:

0.327

Asia WGS

AF:

0.180

AC:

628

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.385

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ART4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over