20-14833444-C-T

Variant names:

• chr20-14833444-C-T
• rs368380
• NM_001351661.2:c.418+148485C>T

Variant summary

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

The NM_001351661.2(MACROD2):​c.418+148485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,868 control chromosomes in the GnomAD database, including 11,402 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 0.37 (11402 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.418+148485C>T		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.418+148485C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.418+148485C>T		intron	N/A	NP_542407.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.418+148485C>T		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000464883.5	TSL:1	n.182-59259C>T		intron	N/A
	MACROD2	ENST00000642719.1		c.418+148485C>T		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56871 AN: 151750 Hom.: 11387 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.375 AC: 56935 AN: 151868 Hom.: 11402 Cov.: 32 AF XY: 0.371 AC XY: 27518 AN XY: 74230

African (AFR) AF: 0.498 AC: 20598 AN: 41402

American (AMR) AF: 0.303 AC: 4627 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1853 AN: 5172

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4806

European-Finnish (FIN) AF: 0.318 AC: 3360 AN: 10564

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23139 AN: 67890

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.350 Hom.: 18588

Bravo AF: 0.382

Asia WGS AF: 0.333 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.37
PhyloP100		0.026
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: rs368380; hg19: chr20-14814090;