rs445251

chr20-15144287-G-Cchr20-15144287-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):c.419-85653G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,906 control chromosomes in the GnomAD database, including 26,556 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 0.59 (26556 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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 (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.419-85653G>C		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.419-85653G>C		intron_variant
MACROD2	NM_080676.6	c.419-85653G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.419-85653G>C		intron_variant			NM_001351661.2	P2
MACROD2	ENST00000217246.8	c.419-85653G>C		intron_variant		2		A2
MACROD2	ENST00000642719.1	c.419-85653G>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89510 AN: 151788 Hom.: 26526 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.590 AC: 89592 AN: 151906 Hom.: 26556 Cov.: 32 AF XY: 0.589 AC XY: 43692 AN XY: 74206

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.584

Alfa AF: 0.459 Hom.: 1214

Bravo AF: 0.591

Asia WGS AF: 0.551 AC: 1914 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.0
Dann	Benign	0.49

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: rs445251; hg19: chr20-15124933;