chr20-14716236-A-C

Variant names:

• chr20-14716236-A-C
• rs6079536
• NM_001351661.2:c.418+31277A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001351661.2(MACROD2):​c.418+31277A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,994 control chromosomes in the GnomAD database, including 21,012 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 0.52 (21012 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+31277A>C		intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.418+31277A>C		intron_variant	Intron 5 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.418+31277A>C		intron_variant	Intron 5 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+31277A>C		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79048 AN: 151876 Hom.: 21003 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.520 AC: 79075 AN: 151994 Hom.: 21012 Cov.: 32 AF XY: 0.516 AC XY: 38356 AN XY: 74278

African (AFR) AF: 0.490 AC: 20309 AN: 41420

American (AMR) AF: 0.434 AC: 6635 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1641 AN: 5166

South Asian (SAS) AF: 0.373 AC: 1796 AN: 4812

European-Finnish (FIN) AF: 0.615 AC: 6487 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38635 AN: 67982

Other (OTH) AF: 0.522 AC: 1102 AN: 2112

Alfa AF: 0.503 Hom.: 3661

Bravo AF: 0.507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		1.7
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: rs6079536; hg19: chr20-14696882; COSMIC: COSV53973943;