rs1020624

chr4-99023703-G-A

Variant summary

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

The NM_015143.3(METAP1):c.115-5164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 985,198 control chromosomes in the GnomAD database, including 270,414 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 0.79 (47443 hom., cov: 32)
  • Exomes 𝑓: 0.73 (222971 hom.)
• Consequence: METAP1 NM_015143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METAP1	NM_015143.3	c.115-5164G>A		intron_variant		ENST00000296411.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METAP1	ENST00000296411.11	c.115-5164G>A		intron_variant		1	NM_015143.3	P1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119424 AN: 152090 Hom.: 47404 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.731 AC: 609014 AN: 832990 Hom.: 222971 Cov.: 33 AF XY: 0.731 AC XY: 281030 AN XY: 384654

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.788

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.846

Gnomad4 FIN exome AF: 0.779

Gnomad4 NFE exome AF: 0.723

Gnomad4 OTH exome AF: 0.757

GnomAD4 genome AF: 0.785 AC: 119518 AN: 152208 Hom.: 47443 Cov.: 32 AF XY: 0.791 AC XY: 58897 AN XY: 74426

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.773

Alfa AF: 0.770 Hom.: 7137

Bravo AF: 0.789

Asia WGS AF: 0.892 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.36

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: rs1020624; hg19: chr4-99944854;