dbSNP rs724820: MACROD2:c.419-143179C>A (chr20-15086761-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001351661.2(MACROD2):c.419-143179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,890 control chromosomes in the GnomAD database, including 11,903 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 0.39 ( 11903 hom., cov: 32)

Consequence

MACROD2
NM_001351661.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Variant links:

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]

MACROD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MACROD2	NM_001351661.2 link	c.419-143179C>A	intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2 link	c.419-143179C>A	intron_variant	Intron 5 of 17		NP_001338592.1
MACROD2	NM_080676.6 link	c.419-143179C>A	intron_variant	Intron 5 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MACROD2	ENST00000684519.1 link	c.419-143179C>A	intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1	A1Z1Q3-1
MACROD2	ENST00000642719.1 link	c.419-143179C>A	intron_variant	Intron 5 of 17			ENSP00000496601.1	A0A2R8YFN3
MACROD2	ENST00000217246.8 link	c.419-143179C>A	intron_variant	Intron 5 of 16	2		ENSP00000217246.4	A1Z1Q3-2

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

58980

AN:

151772

Hom.:

11883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.396

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

GnomAD4 genome

AF:

0.389

AC:

59056

AN:

151890

Hom.:

11903

Cov.:

AF XY:

0.391

AC XY:

29030

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.462

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.536

Gnomad4 SAS

AF:

0.484

Gnomad4 FIN

AF:

0.350

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.396

Alfa

AF:

0.332

Hom.:

7895

Bravo

AF:

0.399

Asia WGS

AF:

0.501

AC:

1744

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.0

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over