rs4141463

Positions:

• chr20-14766825-T-C

Variant summary

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

The NM_001351661.2(MACROD2):​c.418+81866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,988 control chromosomes in the GnomAD database, including 19,730 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 0.50 (19730 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.418+81866T>C		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.418+81866T>C		intron_variant
MACROD2	NM_080676.6	c.418+81866T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+81866T>C		intron_variant			NM_001351661.2	P2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75237 AN: 151868 Hom.: 19717 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.495 AC: 75274 AN: 151988 Hom.: 19730 Cov.: 32 AF XY: 0.491 AC XY: 36470 AN XY: 74302

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.506

Alfa AF: 0.551 Hom.: 34278

Bravo AF: 0.472

Asia WGS AF: 0.295 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.76

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: rs4141463; hg19: chr20-14747471;