rs6074798

Variant names:

• chr20-14781064-G-A
• rs6074798
• NM_001351661.2:c.418+96105G>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+96105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,730 control chromosomes in the GnomAD database, including 13,384 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 0.40 (13384 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 6 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.418+96105G>A		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+96105G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+96105G>A		intron	N/A	NP_542407.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.418+96105G>A		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.181+96105G>A		intron	N/A
	MACROD2	ENST00000642719.1		c.418+96105G>A		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60130 AN: 151610 Hom.: 13383 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.396 AC: 60121 AN: 151730 Hom.: 13384 Cov.: 31 AF XY: 0.395 AC XY: 29261 AN XY: 74132

African (AFR) AF: 0.232 AC: 9601 AN: 41298

American (AMR) AF: 0.344 AC: 5252 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3466

East Asian (EAS) AF: 0.151 AC: 782 AN: 5168

South Asian (SAS) AF: 0.305 AC: 1465 AN: 4800

European-Finnish (FIN) AF: 0.578 AC: 6086 AN: 10534

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34063 AN: 67918

Other (OTH) AF: 0.406 AC: 852 AN: 2098

Alfa AF: 0.450 Hom.: 29030

Bravo AF: 0.369

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.54
PhyloP100		-1.1
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: rs6074798; hg19: chr20-14761710;