rs1544044

Positions:

• chr20-14530522-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.301+37014G>A		intron_variant		ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.301+37014G>A		intron_variant			NP_001338592.1
MACROD2	NM_080676.6	c.301+37014G>A		intron_variant			NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.301+37014G>A		intron_variant			NM_001351661.2	ENSP00000507484	P2

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

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.475

Alfa AF: 0.458 Hom.: 8397

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1544044; hg19: chr20-14511168;