rs6135407

Variant names:

• chr20-15417031-C-T
• rs6135407
• NM_001351661.2:c.541-14374C>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.541-14374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,108 control chromosomes in the GnomAD database, including 1,953 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 0.14 (1953 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 3 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.541-14374C>T		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.541-14374C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.541-14374C>T		intron	N/A	NP_542407.2	A1Z1Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.541-14374C>T		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000402914.5	TSL:1	c.-165-14374C>T		intron	N/A	ENSP00000385290.1	A1Z1Q3-4
	MACROD2	ENST00000642719.1		c.541-14374C>T		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21251 AN: 151990 Hom.: 1942 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.140 AC: 21269 AN: 152108 Hom.: 1953 Cov.: 32 AF XY: 0.142 AC XY: 10554 AN XY: 74332

African (AFR) AF: 0.0335 AC: 1390 AN: 41486

American (AMR) AF: 0.228 AC: 3488 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1078 AN: 5174

South Asian (SAS) AF: 0.133 AC: 642 AN: 4818

European-Finnish (FIN) AF: 0.182 AC: 1927 AN: 10566

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11967 AN: 67982

Other (OTH) AF: 0.133 AC: 282 AN: 2116

Alfa AF: 0.163 Hom.: 1129

Bravo AF: 0.139

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.56
PhyloP100		2.0
Mutation Taster		=95/5	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: rs6135407; hg19: chr20-15397676;