rs6079540

Variant names:

• chr20-14725242-A-G
• rs6079540
• NM_001351661.2:c.418+40283A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-14725242-A-G
• chr20-14725242-A-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.418+40283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,020 control chromosomes in the GnomAD database, including 15,951 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 0.45 (15951 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 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+40283A>G		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+40283A>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+40283A>G		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+40283A>G		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.181+40283A>G		intron	N/A
	MACROD2	ENST00000642719.1		c.418+40283A>G		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68258 AN: 151902 Hom.: 15946 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.449 AC: 68278 AN: 152020 Hom.: 15951 Cov.: 31 AF XY: 0.448 AC XY: 33266 AN XY: 74322

African (AFR) AF: 0.368 AC: 15266 AN: 41454

American (AMR) AF: 0.380 AC: 5802 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3470

East Asian (EAS) AF: 0.271 AC: 1397 AN: 5164

South Asian (SAS) AF: 0.331 AC: 1592 AN: 4814

European-Finnish (FIN) AF: 0.578 AC: 6110 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34942 AN: 67956

Other (OTH) AF: 0.452 AC: 954 AN: 2110

Alfa AF: 0.479 Hom.: 55744

Bravo AF: 0.431

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.17
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: rs6079540; hg19: chr20-14705888;