rs6079537

Variant names:

• chr20-14716740-A-G
• rs6079537
• NM_001351661.2:c.418+31781A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001351661.2(MACROD2):​c.418+31781A>G variant causes a intron change. The variant allele was found at a frequency of 0.389 in 151,928 control chromosomes in the GnomAD database, including 13,337 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 0.39 (13337 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+31781A>G		intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.418+31781A>G		intron_variant	Intron 5 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.418+31781A>G		intron_variant	Intron 5 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+31781A>G		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59184 AN: 151810 Hom.: 13336 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.389 AC: 59174 AN: 151928 Hom.: 13337 Cov.: 31 AF XY: 0.389 AC XY: 28859 AN XY: 74252

African (AFR) AF: 0.184 AC: 7645 AN: 41444

American (AMR) AF: 0.337 AC: 5146 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1647 AN: 3472

East Asian (EAS) AF: 0.203 AC: 1050 AN: 5174

South Asian (SAS) AF: 0.310 AC: 1490 AN: 4808

European-Finnish (FIN) AF: 0.576 AC: 6060 AN: 10520

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34797 AN: 67950

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.465 Hom.: 28601

Bravo AF: 0.362

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		5.4
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: rs6079537; hg19: chr20-14697386;