rs7938819

chr11-64142644-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+8595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,036 control chromosomes in the GnomAD database, including 27,224 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 0.60 (27224 hom., cov: 32)
• Consequence: MACROD1 NM_014067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD1	NM_014067.4	c.517+8595C>T		intron_variant		ENST00000255681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD1	ENST00000255681.7	c.517+8595C>T		intron_variant		1	NM_014067.4	P4
MACROD1	ENST00000675777.1	c.517+8595C>T		intron_variant				A2
MACROD1	ENST00000542359.5	n.298+8595C>T		intron_variant, non_coding_transcript_variant		3
MACROD1	ENST00000545464.5	n.629+8595C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90513 AN: 151918 Hom.: 27209 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.596 AC: 90567 AN: 152036 Hom.: 27224 Cov.: 32 AF XY: 0.598 AC XY: 44417 AN XY: 74318

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.576

Alfa AF: 0.599 Hom.: 3399

Bravo AF: 0.587

Asia WGS AF: 0.546 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
Dann	Benign	0.78

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: rs7938819; hg19: chr11-63910116;