20-15274043-G-C

Variant names:

• chr20-15274043-G-C
• rs367421
• NM_001351661.2:c.540+43982G>C

Variant summary

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

The NM_001351661.2(MACROD2):​c.540+43982G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,118 control chromosomes in the GnomAD database, including 11,456 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 0.38 (11456 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 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.540+43982G>C		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.540+43982G>C		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.540+43982G>C		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.540+43982G>C		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-166+43982G>C		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.540+43982G>C		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57204 AN: 152000 Hom.: 11453 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.376 AC: 57216 AN: 152118 Hom.: 11456 Cov.: 32 AF XY: 0.378 AC XY: 28078 AN XY: 74346

African (AFR) AF: 0.232 AC: 9640 AN: 41488

American (AMR) AF: 0.371 AC: 5676 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1514 AN: 3468

East Asian (EAS) AF: 0.348 AC: 1802 AN: 5174

South Asian (SAS) AF: 0.339 AC: 1631 AN: 4814

European-Finnish (FIN) AF: 0.511 AC: 5400 AN: 10566

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30237 AN: 68006

Other (OTH) AF: 0.388 AC: 821 AN: 2114

Alfa AF: 0.289 Hom.: 816

Bravo AF: 0.358

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.24
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: rs367421; hg19: chr20-15254689; COSMIC: COSV54065167;