ENST00000441595.2:c.-132+1223G>C

Variant names:

• chr10-28328706-C-G
• rs1148186
• ENST00000441595.2:c.-132+1223G>C

Variant summary

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

The ENST00000441595.2(MPP7):​c.-132+1223G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,724 control chromosomes in the GnomAD database, including 6,883 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 0.26 (6883 hom., cov: 31)
• Consequence: MPP7 ENST00000441595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 9 publications found

Genes affected

MPP7 (HGNC:26542): (MAGUK p55 scaffold protein 7) The protein encoded by this gene is a member of the p55 Stardust family of membrane-associated guanylate kinase (MAGUK) proteins, which function in the establishment of epithelial cell polarity. This family member forms a complex with the polarity protein DLG1 (discs, large homolog 1) and facilitates epithelial cell polarity and tight junction formation. Polymorphisms in this gene are associated with variations in site-specific bone mineral density (BMD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP7	XM_047424647.1	c.-132+6164G>C		intron_variant	Intron 1 of 16		XP_047280603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP7	ENST00000441595.2	c.-132+1223G>C		intron_variant	Intron 2 of 11	5		ENSP00000398319.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39027 AN: 151606 Hom.: 6859 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.0386

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.258 AC: 39096 AN: 151724 Hom.: 6883 Cov.: 31 AF XY: 0.254 AC XY: 18854 AN XY: 74126

African (AFR) AF: 0.502 AC: 20740 AN: 41354

American (AMR) AF: 0.161 AC: 2450 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3460

East Asian (EAS) AF: 0.0510 AC: 264 AN: 5174

South Asian (SAS) AF: 0.170 AC: 818 AN: 4818

European-Finnish (FIN) AF: 0.196 AC: 2057 AN: 10486

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11426 AN: 67908

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.151 Hom.: 1053

Bravo AF: 0.266

Asia WGS AF: 0.117 AC: 406 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		0.089

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1148186; hg19: chr10-28617635;