rs1816558

Positions:

• chr3-155125818-G-A
• chr3-155125818-G-T

Variant summary

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

The ENST00000360490.7(MME):​c.720+7007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,732 control chromosomes in the GnomAD database, including 33,781 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 0.67 (33781 hom., cov: 29)
• Consequence: MME ENST00000360490.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

MME (HGNC:7154): (membrane metalloendopeptidase) The protein encoded by this gene is a type II transmembrane glycoprotein and a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). The encoded protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL. This protein is not restricted to leukemic cells, however, and is found on a variety of normal tissues. The protein is a neutral endopeptidase that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. [provided by RefSeq, Aug 2017]

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 = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.720+7007G>A		intron_variant		ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.720+7007G>A		intron_variant		1	NM_007289.4	ENSP00000353679	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 100901 AN: 151614 Hom.: 33752 Cov.: 29

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.665 AC: 100971 AN: 151732 Hom.: 33781 Cov.: 29 AF XY: 0.662 AC XY: 49073 AN XY: 74114

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.677

Alfa AF: 0.694 Hom.: 16808

Bravo AF: 0.670

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.30

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: rs1816558; hg19: chr3-154843607;