rs7272442

Variant names:

• chr20-15294892-G-A
• rs7272442
• NM_001351661.2:c.540+64831G>A

Variant summary

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

The NM_001351661.2(MACROD2):​c.540+64831G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,064 control chromosomes in the GnomAD database, including 19,332 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 0.50 (19332 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.540+64831G>A		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.540+64831G>A		intron_variant	Intron 6 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000402914.5	c.-166+64831G>A		intron_variant	Intron 2 of 13	1		ENSP00000385290.1
MACROD2	ENST00000642719.1	c.540+64831G>A		intron_variant	Intron 6 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.540+64831G>A		intron_variant	Intron 6 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75401 AN: 151944 Hom.: 19300 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.496 AC: 75478 AN: 152064 Hom.: 19332 Cov.: 33 AF XY: 0.492 AC XY: 36591 AN XY: 74328

African (AFR) AF: 0.599 AC: 24828 AN: 41456

American (AMR) AF: 0.414 AC: 6326 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3472

East Asian (EAS) AF: 0.169 AC: 876 AN: 5170

South Asian (SAS) AF: 0.465 AC: 2244 AN: 4824

European-Finnish (FIN) AF: 0.477 AC: 5039 AN: 10564

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33242 AN: 67972

Other (OTH) AF: 0.479 AC: 1011 AN: 2112

Alfa AF: 0.485 Hom.: 13976

Bravo AF: 0.493

Asia WGS AF: 0.331 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.52
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: rs7272442; hg19: chr20-15275538;