rs1225888

Positions:

• chr20-16043580-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001351661.2(MACROD2):​c.1232-991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,952 control chromosomes in the GnomAD database, including 11,662 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 0.35 (11662 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.1232-991A>G		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.1232-991A>G		intron_variant			NM_001351661.2	ENSP00000507484	P2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53506 AN: 151834 Hom.: 11650 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.352 AC: 53514 AN: 151952 Hom.: 11662 Cov.: 32 AF XY: 0.353 AC XY: 26219 AN XY: 74262

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.375

Alfa AF: 0.398 Hom.: 3135

Bravo AF: 0.344

Asia WGS AF: 0.364 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.78

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: rs1225888; hg19: chr20-16024225;