20-15790916-G-A

Variant names:

• chr20-15790916-G-A
• rs6135518
• NM_001351661.2:c.646-71829G>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.646-71829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 151,824 control chromosomes in the GnomAD database, including 318 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 0.030 (318 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.646-71829G>A		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.646-71829G>A		intron_variant	Intron 8 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-60-71829G>A		intron_variant	Intron 4 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.646-71829G>A		intron_variant	Intron 8 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.646-71829G>A		intron_variant	Intron 8 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4486 AN: 151706 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.00503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.00809

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0240

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

GnomAD4 genome AF: 0.0296 AC: 4493 AN: 151824 Hom.: 318 Cov.: 32 AF XY: 0.0333 AC XY: 2469 AN XY: 74164

African (AFR) AF: 0.00501 AC: 208 AN: 41492

American (AMR) AF: 0.0881 AC: 1341 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00809 AC: 28 AN: 3462

East Asian (EAS) AF: 0.290 AC: 1502 AN: 5178

South Asian (SAS) AF: 0.0401 AC: 193 AN: 4812

European-Finnish (FIN) AF: 0.0243 AC: 257 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 914 AN: 67774

Other (OTH) AF: 0.0237 AC: 50 AN: 2106

Alfa AF: 0.0312 Hom.: 30

Bravo AF: 0.0371

Asia WGS AF: 0.118 AC: 410 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.41
PhyloP100		-0.96
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: rs6135518; hg19: chr20-15771561;