20-14347253-G-A

Variant names:

• chr20-14347253-G-A
• rs6079395
• NM_001351661.2:c.272-146226G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.272-146226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,902 control chromosomes in the GnomAD database, including 18,674 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 0.49 (18674 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.272-146226G>A		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.272-146226G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.272-146226G>A		intron	N/A	NP_542407.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.272-146226G>A		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000642719.1		c.272-146226G>A		intron	N/A	ENSP00000496601.1
	MACROD2	ENST00000217246.8	TSL:2	c.272-146226G>A		intron	N/A	ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74110 AN: 151784 Hom.: 18653 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.488 AC: 74189 AN: 151902 Hom.: 18674 Cov.: 31 AF XY: 0.486 AC XY: 36092 AN XY: 74258

African (AFR) AF: 0.439 AC: 18185 AN: 41382

American (AMR) AF: 0.455 AC: 6955 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1814 AN: 3458

East Asian (EAS) AF: 0.204 AC: 1051 AN: 5152

South Asian (SAS) AF: 0.311 AC: 1497 AN: 4806

European-Finnish (FIN) AF: 0.580 AC: 6124 AN: 10552

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36965 AN: 67962

Other (OTH) AF: 0.477 AC: 1005 AN: 2108

Alfa AF: 0.514 Hom.: 90323

Bravo AF: 0.479

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.18
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6079395; hg19: chr20-14327899;