rs3789335

chr20-14339243-G-Achr20-14339243-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):c.272-154236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,064 control chromosomes in the GnomAD database, including 3,057 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 0.20 (3057 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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

Verdict is Benign. Variant got -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 = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.272-154236G>A		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.272-154236G>A		intron_variant
MACROD2	NM_080676.6	c.272-154236G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.272-154236G>A		intron_variant			NM_001351661.2	P2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29764 AN: 151944 Hom.: 3059 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.196 AC: 29766 AN: 152064 Hom.: 3057 Cov.: 32 AF XY: 0.198 AC XY: 14707 AN XY: 74324

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.198

Alfa AF: 0.112 Hom.: 167

Bravo AF: 0.186

Asia WGS AF: 0.295 AC: 1025 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	6.1
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs3789335; hg19: chr20-14319889;