rs11590198

Positions:

• chr1-2620461-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.155-8257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,092 control chromosomes in the GnomAD database, including 3,755 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 0.21 (3755 hom., cov: 32)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMEL1	NM_033467.4	c.155-8257C>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.155-8257C>T		intron_variant		2	NM_033467.4	ENSP00000367668	P1
MMEL1	ENST00000502556.5	c.155-8257C>T		intron_variant		1		ENSP00000422492
MMEL1	ENST00000504800.5	c.155-8257C>T		intron_variant, NMD_transcript_variant		2		ENSP00000425477

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31417 AN: 151974 Hom.: 3743 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.207 AC: 31459 AN: 152092 Hom.: 3755 Cov.: 32 AF XY: 0.215 AC XY: 16014 AN XY: 74362

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.204

Alfa AF: 0.190 Hom.: 3977

Bravo AF: 0.204

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.48

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: rs11590198; hg19: chr1-2551900;