rs1544044

Variant names:

• chr20-14530522-G-A
• rs1544044
• NM_001351661.2:c.301+37014G>A

Variant summary

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

The NM_001351661.2(MACROD2):​c.301+37014G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,988 control chromosomes in the GnomAD database, including 17,568 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 0.48 (17568 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.301+37014G>A		intron_variant	Intron 4 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.301+37014G>A		intron_variant	Intron 4 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.301+37014G>A		intron_variant	Intron 4 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.301+37014G>A		intron_variant	Intron 4 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72418 AN: 151866 Hom.: 17561 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.477 AC: 72470 AN: 151988 Hom.: 17568 Cov.: 32 AF XY: 0.474 AC XY: 35192 AN XY: 74292

African (AFR) AF: 0.541 AC: 22400 AN: 41418

American (AMR) AF: 0.481 AC: 7355 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3466

East Asian (EAS) AF: 0.450 AC: 2324 AN: 5160

South Asian (SAS) AF: 0.285 AC: 1373 AN: 4822

European-Finnish (FIN) AF: 0.468 AC: 4943 AN: 10566

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30743 AN: 67962

Other (OTH) AF: 0.475 AC: 1002 AN: 2110

Alfa AF: 0.459 Hom.: 9361

Bravo AF: 0.486

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.14
PhyloP100		-1.2
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: rs1544044; hg19: chr20-14511168;