4-99046632-T-G

Variant names:

• chr4-99046632-T-G
• rs1230209
• NM_015143.3:c.787+1322T>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.787+1322T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,046 control chromosomes in the GnomAD database, including 3,515 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 0.17 (3515 hom., cov: 30)
• Consequence: METAP1 NM_015143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 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.787+1322T>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.787+1322T>G		intron	N/A	ENSP00000296411.6
	METAP1	ENST00000514051.1	TSL:1	c.121+1322T>G		intron	N/A	ENSP00000422689.1
	METAP1	ENST00000510133.5	TSL:5	c.140-2101T>G		intron	N/A	ENSP00000423071.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26206 AN: 151928 Hom.: 3508 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0706

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.173 AC: 26237 AN: 152046 Hom.: 3515 Cov.: 30 AF XY: 0.180 AC XY: 13398 AN XY: 74332

African (AFR) AF: 0.167 AC: 6920 AN: 41490

American (AMR) AF: 0.257 AC: 3922 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3462

East Asian (EAS) AF: 0.794 AC: 4078 AN: 5138

South Asian (SAS) AF: 0.163 AC: 787 AN: 4822

European-Finnish (FIN) AF: 0.178 AC: 1881 AN: 10566

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7809 AN: 67990

Other (OTH) AF: 0.156 AC: 328 AN: 2108

Alfa AF: 0.142 Hom.: 277

Bravo AF: 0.185

Asia WGS AF: 0.420 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.83
PhyloP100		0.33
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: rs1230209; hg19: chr4-99967783;