chr20-15186129-C-T

Position:

• chr20-15186129-C-T

Variant summary

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

The NM_001351661.2(MACROD2):​c.419-43811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,804 control chromosomes in the GnomAD database, including 13,952 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 0.41 (13952 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.419-43811C>T		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.419-43811C>T		intron_variant
MACROD2	NM_080676.6	c.419-43811C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.419-43811C>T		intron_variant			NM_001351661.2	P2
MACROD2	ENST00000217246.8	c.419-43811C>T		intron_variant		2		A2
MACROD2	ENST00000642719.1	c.419-43811C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61527 AN: 151686 Hom.: 13958 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.405 AC: 61533 AN: 151804 Hom.: 13952 Cov.: 31 AF XY: 0.418 AC XY: 30983 AN XY: 74196

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.402

Alfa AF: 0.420 Hom.: 2680

Bravo AF: 0.390

Asia WGS AF: 0.572 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.067
DANN	Benign	0.45

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: rs6110544; hg19: chr20-15166775;