12-14840674-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021071.4(ART4):c.624C>T(p.Leu208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,800 control chromosomes in the GnomAD database, including 116,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9314 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106726 hom.)
• Consequence: ART4 NM_021071.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267

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]

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

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 12-14840674-G-A is Benign according to our data. Variant chr12-14840674-G-A is described in ClinVar as [Benign]. Clinvar id is 3059324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.267 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ART4	NM_021071.4	c.624C>T	p.Leu208=	synonymous_variant	2/3	ENST00000228936.6
ART4	NM_001354646.2	c.624C>T	p.Leu208=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ART4	ENST00000228936.6	c.624C>T	p.Leu208=	synonymous_variant	2/3	1	NM_021071.4	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51590 AN: 151922 Hom.: 9299 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.354

GnomAD3 exomes AF: 0.347 AC: 87145 AN: 250944 Hom.: 16004 AF XY: 0.356 AC XY: 48291 AN XY: 135606

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.0978

Gnomad SAS exome AF: 0.396

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.377 AC: 550984 AN: 1461760 Hom.: 106726 Cov.: 56 AF XY: 0.378 AC XY: 275199 AN XY: 727168

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.339 AC: 51616 AN: 152040 Hom.: 9314 Cov.: 32 AF XY: 0.336 AC XY: 24972 AN XY: 74320

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.356

Alfa AF: 0.380 Hom.: 21928

Bravo AF: 0.341

Asia WGS AF: 0.244 AC: 853 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.404

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ART4-related disorder Benign:1

Benign, criteria provided, single submitter

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	-0.67
Cadd	Benign	1.1
Dann	Benign	0.83

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: rs3088189; hg19: chr12-14993608; COSMIC: COSV57451388; COSMIC: COSV57451388;