rs4814324

chr20-14762184-C-A

Variant summary

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

The NM_001351661.2(MACROD2):c.418+77225C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,872 control chromosomes in the GnomAD database, including 14,839 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 0.43 (14839 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.418+77225C>A		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.418+77225C>A		intron_variant
MACROD2	NM_080676.6	c.418+77225C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+77225C>A		intron_variant			NM_001351661.2	P2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64782 AN: 151752 Hom.: 14838 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.427 AC: 64791 AN: 151872 Hom.: 14839 Cov.: 32 AF XY: 0.424 AC XY: 31500 AN XY: 74246

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.432

Alfa AF: 0.461 Hom.: 2311

Bravo AF: 0.404

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.7
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: rs4814324; hg19: chr20-14742830;