rs6731583

Positions:

• chr2-201696131-T-C

Variant summary

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

The NM_033066.3(MPP4):​c.-100-2077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,086 control chromosomes in the GnomAD database, including 2,839 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 0.18 (2839 hom., cov: 32)
• Consequence: MPP4 NM_033066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

Genes affected

MPP4 (HGNC:13680): (MAGUK p55 scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) protein family, with an N-terminal PDZ domain, a central src homology 3 region (SH3), and a C-terminal guanylate kinase-like (GUK) domain. The protein is localized to the outer limiting membrane in the retina, and is thought to function in photoreceptor polarity and the organization of specialized intercellular junctions. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPP4	NM_033066.3	c.-100-2077A>G		intron_variant		ENST00000409474.8	NP_149055.2
MPP4	XM_017004620.2	c.-100-2077A>G		intron_variant			XP_016860109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPP4	ENST00000409474.8	c.-100-2077A>G		intron_variant		1	NM_033066.3	ENSP00000387278	P4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27601 AN: 151968 Hom.: 2830 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.182 AC: 27641 AN: 152086 Hom.: 2839 Cov.: 32 AF XY: 0.189 AC XY: 14013 AN XY: 74332

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.178

Alfa AF: 0.156 Hom.: 509

Bravo AF: 0.173

Asia WGS AF: 0.402 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.37

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: rs6731583; hg19: chr2-202560854;