rs367114

Variant names:

• chr20-15582181-C-T
• rs367114
• NM_001351661.2:c.645+82334C>T

Variant summary

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

The NM_001351661.2(MACROD2):​c.645+82334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,764 control chromosomes in the GnomAD database, including 20,518 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 0.50 (20518 hom., cov: 30)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• 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=-1.12).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.645+82334C>T		intron_variant	Intron 8 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.645+82334C>T		intron_variant	Intron 8 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-61+82334C>T		intron_variant	Intron 4 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.645+82334C>T		intron_variant	Intron 8 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.645+82334C>T		intron_variant	Intron 8 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75183 AN: 151646 Hom.: 20501 Cov.: 30

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.496 AC: 75224 AN: 151764 Hom.: 20518 Cov.: 30 AF XY: 0.493 AC XY: 36540 AN XY: 74110

African (AFR) AF: 0.292 AC: 12098 AN: 41364

American (AMR) AF: 0.541 AC: 8253 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.196 AC: 1007 AN: 5148

South Asian (SAS) AF: 0.372 AC: 1788 AN: 4810

European-Finnish (FIN) AF: 0.721 AC: 7549 AN: 10476

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.604 AC: 41035 AN: 67936

Other (OTH) AF: 0.480 AC: 1008 AN: 2102

Alfa AF: 0.559 Hom.: 73183

Bravo AF: 0.479

Asia WGS AF: 0.300 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.26
DANN	Benign	0.66
PhyloP100		-2.6
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: rs367114; hg19: chr20-15562826;