rs6110544

Variant names:

• chr20-15186129-C-T
• rs6110544
• NM_001351661.2:c.419-43811C>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.419-43811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,804 control chromosomes in the GnomAD database, including 13,952 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 0.41 (13952 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.419-43811C>T		intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.419-43811C>T		intron_variant	Intron 5 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.419-43811C>T		intron_variant	Intron 5 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.419-43811C>T		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000642719.1	c.419-43811C>T		intron_variant	Intron 5 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.419-43811C>T		intron_variant	Intron 5 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61527 AN: 151686 Hom.: 13958 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.405 AC: 61533 AN: 151804 Hom.: 13952 Cov.: 31 AF XY: 0.418 AC XY: 30983 AN XY: 74196

African (AFR) AF: 0.209 AC: 8653 AN: 41384

American (AMR) AF: 0.475 AC: 7245 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3468

East Asian (EAS) AF: 0.750 AC: 3868 AN: 5156

South Asian (SAS) AF: 0.520 AC: 2501 AN: 4814

European-Finnish (FIN) AF: 0.570 AC: 5986 AN: 10506

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30115 AN: 67918

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.415 Hom.: 2702

Bravo AF: 0.390

Asia WGS AF: 0.572 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.067
DANN	Benign	0.45
PhyloP100		-2.6
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: rs6110544; hg19: chr20-15166775;