NM_001351661.2:c.541-76297T>C

Variant names:

• chr20-15355108-T-C
• rs6110577
• NM_001351661.2:c.541-76297T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.541-76297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,122 control chromosomes in the GnomAD database, including 3,345 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 0.19 (3345 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.541-76297T>C		intron_variant	Intron 6 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.541-76297T>C		intron_variant	Intron 6 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-165-76297T>C		intron_variant	Intron 2 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.541-76297T>C		intron_variant	Intron 6 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.541-76297T>C		intron_variant	Intron 6 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29162 AN: 152004 Hom.: 3325 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.192 AC: 29210 AN: 152122 Hom.: 3345 Cov.: 32 AF XY: 0.194 AC XY: 14446 AN XY: 74370

African (AFR) AF: 0.267 AC: 11068 AN: 41498

American (AMR) AF: 0.236 AC: 3612 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2433 AN: 5160

South Asian (SAS) AF: 0.186 AC: 897 AN: 4818

European-Finnish (FIN) AF: 0.119 AC: 1264 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8451 AN: 67980

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.160 Hom.: 5148

Bravo AF: 0.211

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.45
PhyloP100		-0.76
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: rs6110577; hg19: chr20-15335754;