rs1676780

chr10-28328881-T-C

Variant summary

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

The ENST00000441595.2(MPP7):c.-132+1048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,224 control chromosomes in the GnomAD database, including 2,091 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 0.16 (2091 hom., cov: 32)
• Consequence: MPP7 ENST00000441595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPP7	XM_047424647.1	c.-132+5989A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPP7	ENST00000441595.2	c.-132+1048A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23777 AN: 152106 Hom.: 2090 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.156 AC: 23780 AN: 152224 Hom.: 2091 Cov.: 32 AF XY: 0.154 AC XY: 11457 AN XY: 74416

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.172

Alfa AF: 0.185 Hom.: 1262

Bravo AF: 0.152

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.3
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1676780; hg19: chr10-28617810;