NM_005925.3:c.2092-623T>C

Variant names:

• chr18-32219608-T-C
• rs7233697
• NM_005925.3:c.2092-623T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005925.3(MEP1B):​c.2092-623T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,064 control chromosomes in the GnomAD database, including 530 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 0.080 (530 hom., cov: 32)
• Consequence: MEP1B NM_005925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 1 publications found

Genes affected

MEP1B (HGNC:7020): (meprin A subunit beta) Meprins are multidomain zinc metalloproteases that are highly expressed in mammalian kidney and intestinal brush border membranes, and in leukocytes and certain cancer cells. They are involved in the hydrolysis of a variety of peptide and protein substrates, and have been implicated in cancer and intestinal inflammation. Mature meprins are oligomers of evolutionarily related, but separately encoded alpha and/or beta subunits. Homooligomers of alpha subunit are secreted, whereas, oligomers containing the beta subunit are plasma membrane-bound. This gene encodes the beta subunit. Targeted disruption of this gene in mice affects embryonic viability, renal gene expression profiles, and distribution of the membrane-associated alpha subunit in kidney and intestine. [provided by RefSeq, Oct 2011]

GAREM1 (HGNC:26136): (GRB2 associated regulator of MAPK1 subtype 1) This gene encodes an adaptor protein which functions in the epidermal growth factor (EGF) receptor-mediated signaling pathway. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEP1B	NM_005925.3	c.2092-623T>C		intron_variant	Intron 14 of 14	ENST00000269202.11	NP_005916.2
MEP1B	NM_001308171.2	c.2092-626T>C		intron_variant	Intron 14 of 14		NP_001295100.1
MEP1B	XM_011526013.3	c.1873-623T>C		intron_variant	Intron 13 of 13		XP_011524315.1
MEP1B	XM_011526014.3	c.1720-623T>C		intron_variant	Intron 12 of 12		XP_011524316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEP1B	ENST00000269202.11	c.2092-623T>C		intron_variant	Intron 14 of 14	1	NM_005925.3	ENSP00000269202.6
MEP1B	ENST00000581447.1	c.2092-626T>C		intron_variant	Intron 14 of 14	1		ENSP00000463280.1
GAREM1	ENST00000583696.1	c.63+67423A>G		intron_variant	Intron 1 of 2	3		ENSP00000464185.1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12107 AN: 151946 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.0808

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0798 AC: 12130 AN: 152064 Hom.: 530 Cov.: 32 AF XY: 0.0810 AC XY: 6017 AN XY: 74318

African (AFR) AF: 0.0670 AC: 2780 AN: 41504

American (AMR) AF: 0.0713 AC: 1089 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0808 AC: 280 AN: 3464

East Asian (EAS) AF: 0.139 AC: 717 AN: 5150

South Asian (SAS) AF: 0.0925 AC: 445 AN: 4812

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10552

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5138 AN: 67986

Other (OTH) AF: 0.0758 AC: 160 AN: 2110

Alfa AF: 0.0780 Hom.: 226

Bravo AF: 0.0763

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.63
PhyloP100		-1.1
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: rs7233697; hg19: chr18-29799571;