chr20-15515663-C-T

Variant names:

• chr20-15515663-C-T
• rs8116068
• NM_001351661.2:c.645+15816C>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+15816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,128 control chromosomes in the GnomAD database, including 2,836 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 0.19 (2836 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.645+15816C>T		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.645+15816C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.645+15816C>T		intron	N/A	NP_542407.2	A1Z1Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.645+15816C>T		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000402914.5	TSL:1	c.-61+15816C>T		intron	N/A	ENSP00000385290.1	A1Z1Q3-4
	MACROD2	ENST00000642719.1		c.645+15816C>T		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28122 AN: 152010 Hom.: 2823 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.185 AC: 28153 AN: 152128 Hom.: 2836 Cov.: 33 AF XY: 0.187 AC XY: 13885 AN XY: 74346

African (AFR) AF: 0.132 AC: 5466 AN: 41510

American (AMR) AF: 0.216 AC: 3305 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3470

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5176

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2694 AN: 10554

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14172 AN: 67996

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.187 Hom.: 407

Bravo AF: 0.178

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.49
PhyloP100		-0.90
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: rs8116068; hg19: chr20-15496308;