rs3890745

chr1-2622185-T-C

Variant summary

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

The NM_033467.4(MMEL1):c.154+7146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,100 control chromosomes in the GnomAD database, including 13,178 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 (13178 hom., cov: 32)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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 = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMEL1	NM_033467.4	c.154+7146A>G		intron_variant		ENST00000378412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMEL1	ENST00000378412.8	c.154+7146A>G		intron_variant		2	NM_033467.4	P1
MMEL1	ENST00000502556.5	c.154+7146A>G		intron_variant		1
MMEL1	ENST00000504800.5	c.154+7146A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61199 AN: 151982 Hom.: 13153 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.403 AC: 61263 AN: 152100 Hom.: 13178 Cov.: 32 AF XY: 0.407 AC XY: 30290 AN XY: 74366

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.369

Alfa AF: 0.333 Hom.: 19305

Bravo AF: 0.408

Asia WGS AF: 0.569 AC: 1979 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	1.3
Dann	Benign	0.23

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: rs3890745; hg19: chr1-2553624;