20-16022761-T-C

Variant names:

• chr20-16022761-T-C
• rs6080100
• NM_001351661.2:c.1154-18440T>C

Variant summary

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

The NM_001351661.2(MACROD2):​c.1154-18440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,072 control chromosomes in the GnomAD database, including 6,126 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 0.27 (6126 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.1154-18440T>C		intron_variant	Intron 15 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.1154-18440T>C		intron_variant	Intron 15 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41208 AN: 151954 Hom.: 6124 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.271 AC: 41242 AN: 152072 Hom.: 6126 Cov.: 32 AF XY: 0.277 AC XY: 20560 AN XY: 74326

African (AFR) AF: 0.154 AC: 6389 AN: 41496

American (AMR) AF: 0.319 AC: 4868 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3466

East Asian (EAS) AF: 0.0746 AC: 386 AN: 5174

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4818

European-Finnish (FIN) AF: 0.397 AC: 4197 AN: 10560

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21885 AN: 67964

Other (OTH) AF: 0.271 AC: 574 AN: 2116

Alfa AF: 0.298 Hom.: 13233

Bravo AF: 0.257

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.57
PhyloP100		-0.16
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: rs6080100; hg19: chr20-16003406;