12-14840920-A-G

Variant names:

• chr12-14840920-A-G
• rs1861698
• NM_021071.4:c.378T>C

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.378T>C​(p.Tyr126Tyr) 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0410
• Publications: 27 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=-0.83).
• BP6: Variant 12-14840920-A-G is Benign according to our data. Variant chr12-14840920-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	NM_021071.4	MANE Select	c.378T>C	p.Tyr126Tyr	synonymous	Exon 2 of 3	NP_066549.2	Q93070
	ART4	NM_001354646.2		c.378T>C	p.Tyr126Tyr	synonymous	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	ENST00000228936.6	TSL:1 MANE Select	c.378T>C	p.Tyr126Tyr	synonymous	Exon 2 of 3	ENSP00000228936.4	Q93070
	ART4	ENST00000420600.2	TSL:1	c.327T>C	p.Tyr109Tyr	synonymous	Exon 2 of 2	ENSP00000405689.1	H7C2G2
	ART4	ENST00000430129.6	TSL:1	c.165+162T>C		intron	N/A	ENSP00000412735.2	Q3KZ30

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48784 AN: 152010 Hom.: 8322 Cov.: 32

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

GnomAD2 exomes AF: 0.317 AC: 79720 AN: 251178 AF XY: 0.321

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 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.: 57 AF XY: 0.353 AC XY: 256863 AN XY: 727234

African (AFR) AF: 0.275 AC: 9191 AN: 33480

American (AMR) AF: 0.338 AC: 15132 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8834 AN: 26136

East Asian (EAS) AF: 0.0894 AC: 3550 AN: 39700

South Asian (SAS) AF: 0.280 AC: 24118 AN: 86258

European-Finnish (FIN) AF: 0.268 AC: 14336 AN: 53410

Middle Eastern (MID) AF: 0.379 AC: 2185 AN: 5768

European-Non Finnish (NFE) AF: 0.379 AC: 421066 AN: 1112002

Other (OTH) AF: 0.334 AC: 20197 AN: 60396

GnomAD4 genome AF: 0.321 AC: 48816 AN: 152128 Hom.: 8334 Cov.: 32 AF XY: 0.315 AC XY: 23446 AN XY: 74360

African (AFR) AF: 0.272 AC: 11264 AN: 41482

American (AMR) AF: 0.351 AC: 5377 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3472

East Asian (EAS) AF: 0.0880 AC: 456 AN: 5184

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4822

European-Finnish (FIN) AF: 0.266 AC: 2820 AN: 10582

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25158 AN: 67962

Other (OTH) AF: 0.325 AC: 687 AN: 2112

Alfa AF: 0.345 Hom.: 14910

Bravo AF: 0.327

Asia WGS AF: 0.180 AC: 628 AN: 3478

EpiCase AF: 0.374

EpiControl AF: 0.385

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	-0.83
CADD	Benign	1.0
DANN	Benign	0.75
PhyloP100		0.041
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: rs1861698; hg19: chr12-14993854; COSMIC: COSV57451395; COSMIC: COSV57451395;