chr1-2622185-T-C

Variant names:

• chr1-2622185-T-C
• rs3890745
• NM_033467.4:c.154+7146A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 100 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033467.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMEL1	NM_033467.4	MANE Select	c.154+7146A>G		intron	N/A	NP_258428.2	Q495T6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMEL1	ENST00000378412.8	TSL:2 MANE Select	c.154+7146A>G		intron	N/A	ENSP00000367668.3	Q495T6-1
	MMEL1	ENST00000502556.5	TSL:1	c.154+7146A>G		intron	N/A	ENSP00000422492.1	Q495T6-3
	MMEL1	ENST00000504800.5	TSL:2	n.154+7146A>G		intron	N/A	ENSP00000425477.1	Q495T6-2

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

African (AFR) AF: 0.537 AC: 22260 AN: 41468

American (AMR) AF: 0.427 AC: 6532 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2638 AN: 5176

South Asian (SAS) AF: 0.482 AC: 2322 AN: 4816

European-Finnish (FIN) AF: 0.361 AC: 3823 AN: 10580

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21616 AN: 67996

Other (OTH) AF: 0.369 AC: 778 AN: 2110

Alfa AF: 0.349 Hom.: 31977

Bravo AF: 0.408

Asia WGS AF: 0.569 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.23
PhyloP100		-1.0
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: rs3890745; hg19: chr1-2553624;