rs6110458

Variant names:

• chr20-14882326-C-T
• rs6110458
• NM_001351661.2:c.418+197367C>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+197367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,018 control chromosomes in the GnomAD database, including 5,046 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 0.25 (5046 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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+197367C>T		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+197367C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+197367C>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+197367C>T		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.182-10377C>T		intron	N/A
	MACROD2	ENST00000642719.1		c.418+197367C>T		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37423 AN: 151900 Hom.: 5042 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.246 AC: 37433 AN: 152018 Hom.: 5046 Cov.: 33 AF XY: 0.244 AC XY: 18102 AN XY: 74292

African (AFR) AF: 0.343 AC: 14195 AN: 41434

American (AMR) AF: 0.190 AC: 2899 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.147 AC: 756 AN: 5148

South Asian (SAS) AF: 0.155 AC: 742 AN: 4802

European-Finnish (FIN) AF: 0.279 AC: 2946 AN: 10578

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14693 AN: 67994

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.216 Hom.: 1926

Bravo AF: 0.243

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.25
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: rs6110458; hg19: chr20-14862972;