rs3088189

Variant names:

• chr12-14840674-G-A
• rs3088189
• NM_021071.4:c.624C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_021071.4(ART4):​c.624C>T​(p.Leu208Leu) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (9314 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106726 hom.)
• Consequence: ART4 NM_021071.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.267
• Publications: 33 publications found

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)

ENSG00000256339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 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 VariationId is 3059324.Status of the report is no_assertion_criteria_provided, 0 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021071.4. 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
	ART4	NM_021071.4	MANE Select	c.624C>T	p.Leu208Leu	synonymous	Exon 2 of 3	NP_066549.2
	ART4	NM_001354646.2		c.624C>T	p.Leu208Leu	synonymous	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	ENST00000228936.6	TSL:1 MANE Select	c.624C>T	p.Leu208Leu	synonymous	Exon 2 of 3	ENSP00000228936.4
	ART4	ENST00000420600.2	TSL:1	c.573C>T	p.Leu191Leu	synonymous	Exon 2 of 2	ENSP00000405689.1
	ART4	ENST00000430129.6	TSL:1	c.165+408C>T		intron	N/A	ENSP00000412735.2

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

GnomAD2 exomes AF: 0.347 AC: 87145 AN: 250944 AF XY: 0.356

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 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

African (AFR) AF: 0.274 AC: 9165 AN: 33478

American (AMR) AF: 0.352 AC: 15738 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9455 AN: 26134

East Asian (EAS) AF: 0.102 AC: 4068 AN: 39698

South Asian (SAS) AF: 0.394 AC: 34024 AN: 86250

European-Finnish (FIN) AF: 0.301 AC: 16085 AN: 53410

Middle Eastern (MID) AF: 0.441 AC: 2542 AN: 5760

European-Non Finnish (NFE) AF: 0.394 AC: 438144 AN: 1111940

Other (OTH) AF: 0.360 AC: 21763 AN: 60390

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

African (AFR) AF: 0.277 AC: 11484 AN: 41488

American (AMR) AF: 0.375 AC: 5721 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3468

East Asian (EAS) AF: 0.0989 AC: 511 AN: 5166

South Asian (SAS) AF: 0.384 AC: 1854 AN: 4826

European-Finnish (FIN) AF: 0.299 AC: 3159 AN: 10556

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26253 AN: 67948

Other (OTH) AF: 0.356 AC: 751 AN: 2112

Alfa AF: 0.373 Hom.: 44890

Bravo AF: 0.341

Asia WGS AF: 0.244 AC: 853 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.404

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ART4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-0.27
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: rs3088189; hg19: chr12-14993608; COSMIC: COSV57451388; COSMIC: COSV57451388;