rs2186571

Variant names:

• chr11-64148228-G-A
• rs2186571
• NM_014067.4:c.517+3011C>T

Variant summary

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

The NM_001411019.1(MACROD1):​c.517+3011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,208 control chromosomes in the GnomAD database, including 389 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 0.064 (389 hom., cov: 32)
• Consequence: MACROD1 NM_001411019.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794
• Publications: 11 publications found

Genes affected

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411019.1. 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
	MACROD1	NM_014067.4	MANE Select	c.517+3011C>T		intron	N/A	NP_054786.2
	MACROD1	NM_001411019.1		c.517+3011C>T		intron	N/A	NP_001397948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+3011C>T		intron	N/A	ENSP00000255681.6
	MACROD1	ENST00000909130.1		c.517+3011C>T		intron	N/A	ENSP00000579189.1
	MACROD1	ENST00000675777.1		c.517+3011C>T		intron	N/A	ENSP00000502549.1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9798 AN: 152090 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0645 AC: 9810 AN: 152208 Hom.: 389 Cov.: 32 AF XY: 0.0647 AC XY: 4816 AN XY: 74412

African (AFR) AF: 0.0395 AC: 1640 AN: 41536

American (AMR) AF: 0.114 AC: 1737 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3470

East Asian (EAS) AF: 0.0415 AC: 215 AN: 5178

South Asian (SAS) AF: 0.123 AC: 596 AN: 4826

European-Finnish (FIN) AF: 0.0504 AC: 534 AN: 10598

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.0676 AC: 4597 AN: 67990

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0750 Hom.: 598

Bravo AF: 0.0673

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.56
PhyloP100		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2186571; hg19: chr11-63915700;