chr20-15196934-A-G

Variant names:

• chr20-15196934-A-G
• rs199307
• ENST00000402914.5:c.-386A>G

Variant summary

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

The NM_001351664.2(MACROD2):​c.-386A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 983,848 control chromosomes in the GnomAD database, including 39,700 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 0.34 (10578 hom., cov: 32)
  • Exomes 𝑓: 0.26 (29122 hom.)
• Consequence: MACROD2 NM_001351664.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351664.2. 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.419-33006A>G		intron	N/A	NP_001338590.1
	MACROD2	NM_001351664.2		c.-386A>G		5_prime_UTR	Exon 1 of 15	NP_001338593.1
	MACROD2	NM_001033087.2		c.-386A>G		5_prime_UTR	Exon 1 of 14	NP_001028259.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000402914.5	TSL:1	c.-386A>G		5_prime_UTR	Exon 1 of 14	ENSP00000385290.1
	MACROD2	ENST00000684519.1	MANE Select	c.419-33006A>G		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000642719.1		c.419-33006A>G		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51144 AN: 151884 Hom.: 10559 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.259 AC: 215398 AN: 831846 Hom.: 29122 Cov.: 30 AF XY: 0.260 AC XY: 99755 AN XY: 384210

African (AFR) AF: 0.621 AC: 9786 AN: 15768

American (AMR) AF: 0.247 AC: 243 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 1212 AN: 5136

East Asian (EAS) AF: 0.0904 AC: 328 AN: 3628

South Asian (SAS) AF: 0.313 AC: 5137 AN: 16436

European-Finnish (FIN) AF: 0.236 AC: 65 AN: 276

Middle Eastern (MID) AF: 0.286 AC: 462 AN: 1614

European-Non Finnish (NFE) AF: 0.251 AC: 190984 AN: 760754

Other (OTH) AF: 0.264 AC: 7181 AN: 27250

GnomAD4 genome AF: 0.337 AC: 51207 AN: 152002 Hom.: 10578 Cov.: 32 AF XY: 0.333 AC XY: 24702 AN XY: 74282

African (AFR) AF: 0.596 AC: 24716 AN: 41442

American (AMR) AF: 0.274 AC: 4183 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.0934 AC: 482 AN: 5158

South Asian (SAS) AF: 0.320 AC: 1541 AN: 4818

European-Finnish (FIN) AF: 0.217 AC: 2291 AN: 10560

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16143 AN: 67978

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.282 Hom.: 12919

Bravo AF: 0.347

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.44
PromoterAI		-0.014	Neutral
Mutation Taster		=300/0	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: rs199307; hg19: chr20-15177580;