20-14886776-G-T

Variant names:

• chr20-14886776-G-T
• rs1475531
• NM_001351661.2:c.418+201817G>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+201817G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,980 control chromosomes in the GnomAD database, including 30,606 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 0.63 (30606 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 9 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]

MACROD2-AS1 (HGNC:37193): (MACROD2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 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+201817G>T		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+201817G>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+201817G>T		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+201817G>T		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.182-5927G>T		intron	N/A
	MACROD2	ENST00000642719.1		c.418+201817G>T		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95425 AN: 151862 Hom.: 30556 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.724

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.629 AC: 95530 AN: 151980 Hom.: 30606 Cov.: 32 AF XY: 0.632 AC XY: 46950 AN XY: 74278

African (AFR) AF: 0.520 AC: 21542 AN: 41432

American (AMR) AF: 0.708 AC: 10811 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2372 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4338 AN: 5150

South Asian (SAS) AF: 0.763 AC: 3677 AN: 4816

European-Finnish (FIN) AF: 0.595 AC: 6286 AN: 10558

Middle Eastern (MID) AF: 0.724 AC: 210 AN: 290

European-Non Finnish (NFE) AF: 0.651 AC: 44282 AN: 67974

Other (OTH) AF: 0.647 AC: 1366 AN: 2110

Alfa AF: 0.653 Hom.: 17412

Bravo AF: 0.634

Asia WGS AF: 0.787 AC: 2734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.51
PhyloP100		-0.047
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: rs1475531; hg19: chr20-14867422;