rs1020624

Variant names:

• chr4-99023703-G-A
• rs1020624
• NM_015143.3:c.115-5164G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• 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 rank	MANE	Protein	UniProt
METAP1	NM_015143.3	c.115-5164G>A		intron_variant	Intron 1 of 10	ENST00000296411.11	NP_055958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METAP1	ENST00000296411.11	c.115-5164G>A		intron_variant	Intron 1 of 10	1	NM_015143.3	ENSP00000296411.6

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

African (AFR) AF: 0.895 AC: 14123 AN: 15786

American (AMR) AF: 0.788 AC: 775 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 3791 AN: 5152

East Asian (EAS) AF: 0.992 AC: 3601 AN: 3630

South Asian (SAS) AF: 0.846 AC: 13928 AN: 16460

European-Finnish (FIN) AF: 0.779 AC: 215 AN: 276

Middle Eastern (MID) AF: 0.808 AC: 1309 AN: 1620

European-Non Finnish (NFE) AF: 0.723 AC: 550609 AN: 761784

Other (OTH) AF: 0.757 AC: 20663 AN: 27298

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

African (AFR) AF: 0.876 AC: 36374 AN: 41538

American (AMR) AF: 0.778 AC: 11892 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2551 AN: 3468

East Asian (EAS) AF: 0.989 AC: 5127 AN: 5186

South Asian (SAS) AF: 0.849 AC: 4101 AN: 4828

European-Finnish (FIN) AF: 0.754 AC: 7981 AN: 10590

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 49003 AN: 67990

Other (OTH) AF: 0.773 AC: 1633 AN: 2112

Alfa AF: 0.773 Hom.: 7437

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
PhyloP100		-1.3
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: rs1020624; hg19: chr4-99944854;