NM_001351661.2:c.418+57404G>A

Variant names:

• chr20-14742363-G-A
• rs6074787
• NM_001351661.2:c.418+57404G>A

Variant summary

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

The NM_001351661.2(MACROD2):​c.418+57404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,892 control chromosomes in the GnomAD database, including 14,132 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 0.41 (14132 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 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.418+57404G>A		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+57404G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+57404G>A		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.418+57404G>A		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.181+57404G>A		intron	N/A
	MACROD2	ENST00000642719.1		c.418+57404G>A		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62440 AN: 151772 Hom.: 14132 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.411 AC: 62449 AN: 151892 Hom.: 14132 Cov.: 32 AF XY: 0.409 AC XY: 30390 AN XY: 74232

African (AFR) AF: 0.263 AC: 10908 AN: 41430

American (AMR) AF: 0.344 AC: 5258 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1688 AN: 3470

East Asian (EAS) AF: 0.152 AC: 788 AN: 5170

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4826

European-Finnish (FIN) AF: 0.578 AC: 6071 AN: 10496

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34816 AN: 67910

Other (OTH) AF: 0.421 AC: 889 AN: 2112

Alfa AF: 0.476 Hom.: 21963

Bravo AF: 0.385

Asia WGS AF: 0.229 AC: 795 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.30
PhyloP100		0.49
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: rs6074787; hg19: chr20-14723009;