20-15504503-C-T

Variant names:

• chr20-15504503-C-T
• rs6079855
• NM_001351661.2:c.645+4656C>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.645+4656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,056 control chromosomes in the GnomAD database, including 40,941 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 0.73 (40941 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 2 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.645+4656C>T		intron_variant	Intron 8 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.645+4656C>T		intron_variant	Intron 8 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-61+4656C>T		intron_variant	Intron 4 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.645+4656C>T		intron_variant	Intron 8 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.645+4656C>T		intron_variant	Intron 8 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111288 AN: 151938 Hom.: 40913 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.732 AC: 111360 AN: 152056 Hom.: 40941 Cov.: 32 AF XY: 0.731 AC XY: 54276 AN XY: 74296

African (AFR) AF: 0.787 AC: 32650 AN: 41478

American (AMR) AF: 0.765 AC: 11689 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3468

East Asian (EAS) AF: 0.736 AC: 3812 AN: 5180

South Asian (SAS) AF: 0.627 AC: 3013 AN: 4808

European-Finnish (FIN) AF: 0.677 AC: 7139 AN: 10540

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48172 AN: 67986

Other (OTH) AF: 0.728 AC: 1538 AN: 2112

Alfa AF: 0.711 Hom.: 30050

Bravo AF: 0.740

Asia WGS AF: 0.640 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.20
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: rs6079855; hg19: chr20-15485148;