rs4814386

Variant names:

• chr20-15490644-C-T
• rs4814386
• NM_001351661.2:c.572-9130C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.572-9130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,956 control chromosomes in the GnomAD database, including 28,036 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (28036 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 2 publications found

Genes affected

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351661.2. 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
	MACROD2	NM_001351661.2	MANE Select	c.572-9130C>T		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.572-9130C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.572-9130C>T		intron	N/A	NP_542407.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.572-9130C>T		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-134-9130C>T		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.572-9130C>T		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88592 AN: 151838 Hom.: 28034 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.583 AC: 88614 AN: 151956 Hom.: 28036 Cov.: 31 AF XY: 0.582 AC XY: 43233 AN XY: 74278

African (AFR) AF: 0.316 AC: 13069 AN: 41400

American (AMR) AF: 0.669 AC: 10202 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2418 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3560 AN: 5156

South Asian (SAS) AF: 0.566 AC: 2716 AN: 4802

European-Finnish (FIN) AF: 0.638 AC: 6756 AN: 10582

Middle Eastern (MID) AF: 0.645 AC: 187 AN: 290

European-Non Finnish (NFE) AF: 0.702 AC: 47715 AN: 67990

Other (OTH) AF: 0.634 AC: 1339 AN: 2112

Alfa AF: 0.628 Hom.: 3903

Bravo AF: 0.573

Asia WGS AF: 0.548 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.46
PhyloP100		-0.94
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: rs4814386; hg19: chr20-15471289;