rs2186571

Positions:

• chr11-64148228-G-A

Variant summary

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

The NM_014067.4(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_014067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD1	NM_014067.4	c.517+3011C>T		intron_variant		ENST00000255681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD1	ENST00000255681.7	c.517+3011C>T		intron_variant		1	NM_014067.4	P4
MACROD1	ENST00000675777.1	c.517+3011C>T		intron_variant				A2
MACROD1	ENST00000542359.5	n.298+3011C>T		intron_variant, non_coding_transcript_variant		3
MACROD1	ENST00000545464.5	n.629+3011C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.0415

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.0676

Gnomad4 OTH AF: 0.0806

Alfa AF: 0.0758 Hom.: 449

Bravo AF: 0.0673

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2186571; hg19: chr11-63915700;