20-14833444-C-T

Position:

• chr20-14833444-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.418+148485C>T		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.418+148485C>T		intron_variant
MACROD2	NM_080676.6	c.418+148485C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+148485C>T		intron_variant			NM_001351661.2	P2

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

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.340

Alfa AF: 0.336 Hom.: 10836

Bravo AF: 0.382

Asia WGS AF: 0.333 AC: 1163 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	4.5
DANN	Benign	0.37

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: rs368380; hg19: chr20-14814090;