rs453573

Variant names:

• chr20-15583469-C-T
• rs453573
• NM_001351661.2:c.645+83622C>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.645+83622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,960 control chromosomes in the GnomAD database, including 34,978 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 0.67 (34978 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.645+83622C>T		intron_variant	Intron 8 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.645+83622C>T		intron_variant	Intron 8 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-61+83622C>T		intron_variant	Intron 4 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.645+83622C>T		intron_variant	Intron 8 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.645+83622C>T		intron_variant	Intron 8 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102018 AN: 151842 Hom.: 34929 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.672 AC: 102123 AN: 151960 Hom.: 34978 Cov.: 31 AF XY: 0.669 AC XY: 49682 AN XY: 74244

African (AFR) AF: 0.791 AC: 32824 AN: 41478

American (AMR) AF: 0.648 AC: 9891 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3466

East Asian (EAS) AF: 0.480 AC: 2464 AN: 5136

South Asian (SAS) AF: 0.570 AC: 2742 AN: 4810

European-Finnish (FIN) AF: 0.730 AC: 7711 AN: 10568

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.627 AC: 42574 AN: 67928

Other (OTH) AF: 0.621 AC: 1311 AN: 2110

Alfa AF: 0.636 Hom.: 53809

Bravo AF: 0.674

Asia WGS AF: 0.546 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.94
DANN	Benign	0.80
PhyloP100		-0.45
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: rs453573; hg19: chr20-15564114;