rs6043422

Variant names:

• chr20-15668721-G-A
• rs6043422
• NM_001351661.2:c.645+168874G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-15668721-G-A
• chr20-15668721-G-C
• chr20-15668721-G-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+168874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,940 control chromosomes in the GnomAD database, including 23,952 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 0.56 (23952 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 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+168874G>A		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.645+168874G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.645+168874G>A		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+168874G>A		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000402914.5	TSL:1	c.-61+168874G>A		intron	N/A	ENSP00000385290.1	A1Z1Q3-4
	MACROD2	ENST00000642719.1		c.645+168874G>A		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84459 AN: 151822 Hom.: 23926 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.556 AC: 84544 AN: 151940 Hom.: 23952 Cov.: 32 AF XY: 0.563 AC XY: 41833 AN XY: 74302

African (AFR) AF: 0.551 AC: 22815 AN: 41398

American (AMR) AF: 0.612 AC: 9355 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3462

East Asian (EAS) AF: 0.851 AC: 4395 AN: 5166

South Asian (SAS) AF: 0.662 AC: 3186 AN: 4814

European-Finnish (FIN) AF: 0.552 AC: 5829 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35827 AN: 67956

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.530 Hom.: 66371

Bravo AF: 0.558

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-1.5
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: rs6043422; hg19: chr20-15649366; COSMIC: COSV54060727;