rs6135518

Positions:

• chr20-15790916-G-A
• chr20-15790916-G-C

Variant summary

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

The NM_001351661.2(MACROD2):​c.646-71829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 151,824 control chromosomes in the GnomAD database, including 318 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 0.030 (318 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.646-71829G>A		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.646-71829G>A		intron_variant			NM_001351661.2	ENSP00000507484	P2
MACROD2	ENST00000402914.5	c.-60-71829G>A		intron_variant		1		ENSP00000385290
MACROD2	ENST00000217246.8	c.646-71829G>A		intron_variant		2		ENSP00000217246	A2
MACROD2	ENST00000642719.1	c.646-71829G>A		intron_variant				ENSP00000496601	A2

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4486 AN: 151706 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.00503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.00809

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0240

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

GnomAD4 genome AF: 0.0296 AC: 4493 AN: 151824 Hom.: 318 Cov.: 32 AF XY: 0.0333 AC XY: 2469 AN XY: 74164

Gnomad4 AFR AF: 0.00501

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.00809

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.0401

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0312 Hom.: 30

Bravo AF: 0.0371

Asia WGS AF: 0.118 AC: 410 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.41

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: rs6135518; hg19: chr20-15771561;