ENST00000441595.2:c.-132+1048A>G

Variant names:

• chr10-28328881-T-C
• rs1676780
• ENST00000441595.2:c.-132+1048A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.8).
• 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 rank	MANE	Protein	UniProt
MPP7	XM_047424647.1	c.-132+5989A>G		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+1048A>G		intron_variant	Intron 2 of 11	5		ENSP00000398319.1

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

African (AFR) AF: 0.101 AC: 4199 AN: 41554

American (AMR) AF: 0.150 AC: 2296 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5178

South Asian (SAS) AF: 0.121 AC: 585 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1719 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13556 AN: 67986

Other (OTH) AF: 0.172 AC: 365 AN: 2116

Alfa AF: 0.185 Hom.: 1414

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
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs1676780; hg19: chr10-28617810;