rs1037475

Positions:

• chr4-99031559-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015143.3(METAP1):​c.166+2641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,286,878 control chromosomes in the GnomAD database, including 203,240 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 0.47 (18543 hom., cov: 32)
  • Exomes 𝑓: 0.57 (184697 hom.)
• Consequence: METAP1 NM_015143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METAP1	NM_015143.3	c.166+2641A>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.166+2641A>G		intron_variant		1	NM_015143.3	ENSP00000296411	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72135 AN: 151966 Hom.: 18546 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.504

GnomAD3 exomes AF: 0.516 AC: 66198 AN: 128330 Hom.: 18491 AF XY: 0.537 AC XY: 37773 AN XY: 70284

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.693

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.565 AC: 641549 AN: 1134794 Hom.: 184697 Cov.: 39 AF XY: 0.571 AC XY: 317957 AN XY: 556808

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.592

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.474 AC: 72158 AN: 152084 Hom.: 18543 Cov.: 32 AF XY: 0.477 AC XY: 35454 AN XY: 74340

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.504

Alfa AF: 0.549 Hom.: 49925

Bravo AF: 0.452

Asia WGS AF: 0.445 AC: 1545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1037475; hg19: chr4-99952710; COSMIC: COSV56445753;