chr4-99046540-T-C

Variant names:

• chr4-99046540-T-C
• rs1230210
• NM_015143.3:c.787+1230T>C

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+1230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,172 control chromosomes in the GnomAD database, including 47,899 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 (47899 hom., cov: 33)
• Consequence: METAP1 NM_015143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 4 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=-0.94).
• 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.787+1230T>C		intron_variant	Intron 8 of 10	ENST00000296411.11	NP_055958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METAP1	ENST00000296411.11	c.787+1230T>C		intron_variant	Intron 8 of 10	1	NM_015143.3	ENSP00000296411.6
METAP1	ENST00000514051.1	c.121+1230T>C		intron_variant	Intron 1 of 2	1		ENSP00000422689.1
METAP1	ENST00000510133.5	c.140-2193T>C		intron_variant	Intron 1 of 3	5		ENSP00000423071.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119911 AN: 152054 Hom.: 47848 Cov.: 33

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.789 AC: 120020 AN: 152172 Hom.: 47899 Cov.: 33 AF XY: 0.795 AC XY: 59116 AN XY: 74392

African (AFR) AF: 0.891 AC: 36998 AN: 41538

American (AMR) AF: 0.777 AC: 11878 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2548 AN: 3468

East Asian (EAS) AF: 0.989 AC: 5121 AN: 5180

South Asian (SAS) AF: 0.843 AC: 4062 AN: 4818

European-Finnish (FIN) AF: 0.754 AC: 7976 AN: 10578

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48949 AN: 67996

Other (OTH) AF: 0.774 AC: 1631 AN: 2108

Alfa AF: 0.744 Hom.: 130758

Bravo AF: 0.793

Asia WGS AF: 0.894 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.70
PhyloP100		-1.9
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: rs1230210; hg19: chr4-99967691;