4-99046632-T-G

Position:

• chr4-99046632-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METAP1	NM_015143.3	c.787+1322T>G		intron_variant		ENST00000296411.11	NP_055958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METAP1	ENST00000296411.11	c.787+1322T>G		intron_variant		1	NM_015143.3	ENSP00000296411.6
METAP1	ENST00000514051.1	c.121+1322T>G		intron_variant		1		ENSP00000422689.1
METAP1	ENST00000510133.5	c.140-2101T>G		intron_variant		5		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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.156

Alfa AF: 0.140 Hom.: 262

Bravo AF: 0.185

Asia WGS AF: 0.420 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.83

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: rs1230209; hg19: chr4-99967783;