rs6684865

Positions:

• chr1-2614790-G-A

Variant summary

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

The NM_033467.4(MMEL1):​c.155-2586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 150,996 control chromosomes in the GnomAD database, including 12,524 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 0.40 (12524 hom., cov: 30)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

Genes affected

MMEL1 (HGNC:14668): (membrane metalloendopeptidase like 1) The protein encoded by this gene is a member of the neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mainly in testis with weak expression in the brain, kidney, and heart. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMEL1	NM_033467.4	c.155-2586C>T		intron_variant		ENST00000378412.8	NP_258428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMEL1	ENST00000378412.8	c.155-2586C>T		intron_variant		2	NM_033467.4	ENSP00000367668.3
MMEL1	ENST00000502556.5	c.155-2586C>T		intron_variant		1		ENSP00000422492.1
MMEL1	ENST00000504800.5	n.155-2586C>T		intron_variant		2		ENSP00000425477.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 59742 AN: 150880 Hom.: 12505 Cov.: 30

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.396 AC: 59789 AN: 150996 Hom.: 12524 Cov.: 30 AF XY: 0.400 AC XY: 29513 AN XY: 73710

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.366

Alfa AF: 0.332 Hom.: 8676

Bravo AF: 0.401

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.61

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: rs6684865; hg19: chr1-2546229;