rs8121515

Variant names:

• chr20-15454036-A-G
• rs8121515
• NM_001351661.2:c.571+22601A>G

Variant summary

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

The NM_001351661.2(MACROD2):​c.571+22601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,128 control chromosomes in the GnomAD database, including 636 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 0.076 (636 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• Publications: 0 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.571+22601A>G		intron_variant	Intron 7 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.571+22601A>G		intron_variant	Intron 7 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-135+22601A>G		intron_variant	Intron 3 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.571+22601A>G		intron_variant	Intron 7 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.571+22601A>G		intron_variant	Intron 7 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11607 AN: 152010 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0588

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

GnomAD4 genome AF: 0.0765 AC: 11636 AN: 152128 Hom.: 636 Cov.: 32 AF XY: 0.0756 AC XY: 5627 AN XY: 74384

African (AFR) AF: 0.157 AC: 6518 AN: 41490

American (AMR) AF: 0.0413 AC: 631 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.0565 AC: 291 AN: 5154

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4816

European-Finnish (FIN) AF: 0.0545 AC: 578 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0446 AC: 3034 AN: 67996

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0588 Hom.: 159

Bravo AF: 0.0780

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		0.52
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: rs8121515; hg19: chr20-15434681;