rs871044

chr18-11907375-A-G

Variant summary

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

The NM_023075.6(MPPE1):c.-200+826T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,018 control chromosomes in the GnomAD database, including 19,274 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 0.49 (19274 hom., cov: 32)
• Consequence: MPPE1 NM_023075.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

Genes affected

MPPE1 (HGNC:15988): (metallophosphoesterase 1) Predicted to enable GPI anchor binding activity; GPI-mannose ethanolamine phosphate phosphodiesterase activity; and manganese ion binding activity. Involved in GPI anchor biosynthetic process. Located in Golgi apparatus and nucleoplasm. [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 (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPPE1	NM_023075.6	c.-200+826T>C		intron_variant		ENST00000588072.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPPE1	ENST00000588072.6	c.-200+826T>C		intron_variant		1	NM_023075.6	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74265 AN: 151900 Hom.: 19248 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.489 AC: 74344 AN: 152018 Hom.: 19274 Cov.: 32 AF XY: 0.486 AC XY: 36118 AN XY: 74306

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.504

Alfa AF: 0.425 Hom.: 20053

Bravo AF: 0.502

Asia WGS AF: 0.476 AC: 1655 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	6.7
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs871044; hg19: chr18-11907374;