rs4814386

Positions:

• chr20-15490644-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.572-9130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,956 control chromosomes in the GnomAD database, including 28,036 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 0.58 (28036 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.572-9130C>T		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.572-9130C>T		intron_variant			NM_001351661.2	ENSP00000507484	P2
MACROD2	ENST00000402914.5	c.-134-9130C>T		intron_variant		1		ENSP00000385290
MACROD2	ENST00000217246.8	c.572-9130C>T		intron_variant		2		ENSP00000217246	A2
MACROD2	ENST00000642719.1	c.572-9130C>T		intron_variant				ENSP00000496601	A2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88592 AN: 151838 Hom.: 28034 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.583 AC: 88614 AN: 151956 Hom.: 28036 Cov.: 31 AF XY: 0.582 AC XY: 43233 AN XY: 74278

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.634

Alfa AF: 0.628 Hom.: 3903

Bravo AF: 0.573

Asia WGS AF: 0.548 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.46

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: rs4814386; hg19: chr20-15471289;