rs1676780

Variant names:

• chr10-28328881-T-C
• rs1676780
• ENST00000893162.1:c.-132+5989A>G

Variant summary

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

The ENST00000893162.1(MPP7):​c.-132+5989A>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 ENST00000893162.1 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000893162.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP7	ENST00000893162.1		c.-132+5989A>G		intron	N/A	ENSP00000563221.1
	MPP7	ENST00000957212.1		c.-235+5989A>G		intron	N/A	ENSP00000627271.1
	MPP7	ENST00000441595.2	TSL:5	c.-132+1048A>G		intron	N/A	ENSP00000398319.1	U5GXS2

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1676780;

hg19: chr10-28617810;