20-14751960-C-T

Variant names:

• chr20-14751960-C-T
• rs6079553
• NM_001351661.2:c.418+67001C>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+67001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,596 control chromosomes in the GnomAD database, including 13,740 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 0.40 (13740 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.505 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+67001C>T		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+67001C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+67001C>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+67001C>T		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.181+67001C>T		intron	N/A
	MACROD2	ENST00000642719.1		c.418+67001C>T		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61268 AN: 151476 Hom.: 13740 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.404 AC: 61269 AN: 151596 Hom.: 13740 Cov.: 31 AF XY: 0.402 AC XY: 29791 AN XY: 74096

African (AFR) AF: 0.249 AC: 10283 AN: 41330

American (AMR) AF: 0.340 AC: 5186 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1631 AN: 3460

East Asian (EAS) AF: 0.152 AC: 786 AN: 5160

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4800

European-Finnish (FIN) AF: 0.574 AC: 6007 AN: 10458

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34522 AN: 67818

Other (OTH) AF: 0.413 AC: 868 AN: 2104

Alfa AF: 0.473 Hom.: 8741

Bravo AF: 0.378

Asia WGS AF: 0.228 AC: 796 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	0.34
DANN	Benign	0.21
PhyloP100		-0.39
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: rs6079553; hg19: chr20-14732606;