rs6131684

Positions:

• chr20-15643511-A-G

Variant summary

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

The NM_001351661.2(MACROD2):​c.645+143664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,996 control chromosomes in the GnomAD database, including 15,774 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 0.43 (15774 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.645+143664A>G		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.645+143664A>G		intron_variant			NM_001351661.2	ENSP00000507484	P2
MACROD2	ENST00000402914.5	c.-61+143664A>G		intron_variant		1		ENSP00000385290
MACROD2	ENST00000217246.8	c.645+143664A>G		intron_variant		2		ENSP00000217246	A2
MACROD2	ENST00000642719.1	c.645+143664A>G		intron_variant				ENSP00000496601	A2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64653 AN: 151878 Hom.: 15777 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.425 AC: 64668 AN: 151996 Hom.: 15774 Cov.: 33 AF XY: 0.427 AC XY: 31746 AN XY: 74272

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.428

Alfa AF: 0.489 Hom.: 11829

Bravo AF: 0.410

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.044
DANN	Benign	0.71

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: rs6131684; hg19: chr20-15624156;