chr20-14875571-T-A

Variant names:

• chr20-14875571-T-A
• rs1536898
• NM_001351661.2:c.418+190612T>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.418+190612T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,144 control chromosomes in the GnomAD database, including 62,861 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 0.91 (62861 hom., cov: 30)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+190612T>A		intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.418+190612T>A		intron_variant	Intron 5 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.418+190612T>A		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+190612T>A		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137977 AN: 152026 Hom.: 62798 Cov.: 30

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.908 AC: 138099 AN: 152144 Hom.: 62861 Cov.: 30 AF XY: 0.908 AC XY: 67508 AN XY: 74372

African (AFR) AF: 0.977 AC: 40572 AN: 41520

American (AMR) AF: 0.909 AC: 13893 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5141 AN: 5158

South Asian (SAS) AF: 0.908 AC: 4374 AN: 4818

European-Finnish (FIN) AF: 0.872 AC: 9230 AN: 10584

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59043 AN: 68000

Other (OTH) AF: 0.894 AC: 1887 AN: 2110

Alfa AF: 0.834 Hom.: 2513

Bravo AF: 0.915

Asia WGS AF: 0.952 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.64
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: rs1536898; hg19: chr20-14856217;