rs6043472

Positions:

• chr20-15707221-C-A
• chr20-15707221-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.646-155524C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,008 control chromosomes in the GnomAD database, including 7,869 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 0.29 (7869 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.646-155524C>A		intron_variant		ENST00000684519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.646-155524C>A		intron_variant			NM_001351661.2	P2
MACROD2	ENST00000402914.5	c.-60-155524C>A		intron_variant		1
MACROD2	ENST00000217246.8	c.646-155524C>A		intron_variant		2		A2
MACROD2	ENST00000642719.1	c.646-155524C>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43666 AN: 151890 Hom.: 7857 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.288 AC: 43711 AN: 152008 Hom.: 7869 Cov.: 32 AF XY: 0.284 AC XY: 21099 AN XY: 74316

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.270

Alfa AF: 0.225 Hom.: 2721

Bravo AF: 0.302

Asia WGS AF: 0.272 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs6043472; hg19: chr20-15687866;