4-99029330-A-G

Variant names:

• chr4-99029330-A-G
• rs10489131
• NM_015143.3:c.166+412A>G

Variant summary

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

The NM_015143.3(METAP1):​c.166+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,140 control chromosomes in the GnomAD database, including 1,199 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 0.078 (1199 hom., cov: 32)
• Consequence: METAP1 NM_015143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 1 publications found

Genes affected

METAP1 (HGNC:15789): (methionyl aminopeptidase 1) Predicted to enable aminopeptidase activity and metalloexopeptidase activity. Involved in platelet aggregation. Predicted to be located in cytosol. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015143.3. 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
	METAP1	NM_015143.3	MANE Select	c.166+412A>G		intron	N/A	NP_055958.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METAP1	ENST00000296411.11	TSL:1 MANE Select	c.166+412A>G		intron	N/A	ENSP00000296411.6
	METAP1	ENST00000503247.5	TSL:5	n.*121+412A>G		intron	N/A	ENSP00000424462.1
	METAP1	ENST00000506238.5	TSL:4	n.*117+412A>G		intron	N/A	ENSP00000426702.1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11939 AN: 152022 Hom.: 1199 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0488

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0784 AC: 11930 AN: 152140 Hom.: 1199 Cov.: 32 AF XY: 0.0849 AC XY: 6314 AN XY: 74384

African (AFR) AF: 0.0581 AC: 2412 AN: 41520

American (AMR) AF: 0.101 AC: 1538 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0488 AC: 169 AN: 3464

East Asian (EAS) AF: 0.569 AC: 2942 AN: 5170

South Asian (SAS) AF: 0.110 AC: 533 AN: 4824

European-Finnish (FIN) AF: 0.106 AC: 1123 AN: 10580

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3019 AN: 67976

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0618 Hom.: 203

Bravo AF: 0.0787

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.77
PhyloP100		-0.69
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: rs10489131; hg19: chr4-99950481;