rs7233697

chr18-32219608-T-Cchr18-32219608-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MEP1B	NM_005925.3	c.2092-623T>C		intron_variant		ENST00000269202.11
MEP1B	NM_001308171.2	c.2092-626T>C		intron_variant
MEP1B	XM_011526013.3	c.1873-623T>C		intron_variant
MEP1B	XM_011526014.3	c.1720-623T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEP1B	ENST00000269202.11	c.2092-623T>C		intron_variant		1	NM_005925.3	P4
MEP1B	ENST00000581447.1	c.2092-626T>C		intron_variant		1		A1
GAREM1	ENST00000583696.1	c.65+67423A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.0808

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0785 Hom.: 132

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

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: rs7233697; hg19: chr18-29799571;