chr1-2608093-A-G

Position:

• chr1-2608093-A-G

Variant summary

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

The NM_033467.4(MMEL1):​c.536-1024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,968 control chromosomes in the GnomAD database, including 16,838 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 0.45 (16838 hom., cov: 33)
• Consequence: MMEL1 NM_033467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738

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 = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMEL1	NM_033467.4	c.536-1024T>C		intron_variant		ENST00000378412.8	NP_258428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMEL1	ENST00000378412.8	c.536-1024T>C		intron_variant		2	NM_033467.4	ENSP00000367668	P1
MMEL1	ENST00000502556.5	c.480+1301T>C		intron_variant		1		ENSP00000422492
MMEL1	ENST00000504800.5	c.536-1024T>C		intron_variant, NMD_transcript_variant		2		ENSP00000425477
MMEL1	ENST00000509374.1	n.365-1024T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68257 AN: 151850 Hom.: 16797 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.450 AC: 68348 AN: 151968 Hom.: 16838 Cov.: 33 AF XY: 0.453 AC XY: 33679 AN XY: 74272

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.408

Alfa AF: 0.394 Hom.: 1618

Bravo AF: 0.458

Asia WGS AF: 0.592 AC: 2061 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	3.0
DANN	Benign	0.46

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: rs10910108; hg19: chr1-2539532; COSMIC: COSV56524611;