rs10485530

Variant names:

• chr20-15579471-A-G
• rs10485530
• NM_001351661.2:c.645+79624A>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.645+79624A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,200 control chromosomes in the GnomAD database, including 719 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 0.078 (719 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.645+79624A>G		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+79624A>G		intron_variant	Intron 8 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-61+79624A>G		intron_variant	Intron 4 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.645+79624A>G		intron_variant	Intron 8 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.645+79624A>G		intron_variant	Intron 8 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11917 AN: 152080 Hom.: 714 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0784 AC: 11939 AN: 152200 Hom.: 719 Cov.: 32 AF XY: 0.0779 AC XY: 5795 AN XY: 74406

African (AFR) AF: 0.160 AC: 6649 AN: 41510

American (AMR) AF: 0.0932 AC: 1425 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.164 AC: 844 AN: 5156

South Asian (SAS) AF: 0.0464 AC: 224 AN: 4824

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2143 AN: 68018

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0433 Hom.: 257

Bravo AF: 0.0897

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		0.14
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: rs10485530; hg19: chr20-15560116;