rs7938819

Variant names:

• chr11-64142644-G-A
• rs7938819
• NM_014067.4:c.517+8595C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD1	NM_014067.4	MANE Select	c.517+8595C>T		intron	N/A	NP_054786.2
	MACROD1	NM_001411019.1		c.517+8595C>T		intron	N/A	NP_001397948.1	A0A6Q8PH91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+8595C>T		intron	N/A	ENSP00000255681.6	Q9BQ69
	MACROD1	ENST00000909130.1		c.517+8595C>T		intron	N/A	ENSP00000579189.1
	MACROD1	ENST00000675777.1		c.517+8595C>T		intron	N/A	ENSP00000502549.1	A0A6Q8PH91

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

African (AFR) AF: 0.638 AC: 26432 AN: 41446

American (AMR) AF: 0.488 AC: 7445 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2315 AN: 3468

East Asian (EAS) AF: 0.656 AC: 3384 AN: 5162

South Asian (SAS) AF: 0.593 AC: 2858 AN: 4818

European-Finnish (FIN) AF: 0.649 AC: 6866 AN: 10576

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39265 AN: 67984

Other (OTH) AF: 0.576 AC: 1214 AN: 2108

Alfa AF: 0.601 Hom.: 3562

Bravo AF: 0.587

Asia WGS AF: 0.546 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.15
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: rs7938819; hg19: chr11-63910116;