chr15-41810717-CAAAAAAAAAAAA-C

Variant names:

• chr15-41810717-CAAAAAAAAAAAA-C
• rs58612719
• NM_014994.3:c.207-155_207-144delAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014994.3(MAPKBP1):​c.207-155_207-144delAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000863 in 347,806 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000086 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKBP1 NM_014994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

Genes affected

MAPKBP1 (HGNC:29536): (mitogen-activated protein kinase binding protein 1) This gene encodes a scaffold protein that regulates the JNK (c-Jun N-terminal kinase) and NOD2 (nucleotide-binding oligomerization domain-containing protein 2) signaling pathways. The encoded protein interacts with another related JNK pathway scaffold protein, WDR62, via a conserved dimerization domain, and enhances JNK signaling. This protein may play a role in bacterial immunity by binding to the NOD2 receptor and negatively regulating downstream antibacterial and pro-inflammatory signaling. Mutations in this gene that impair cellular localization of the encoded protein cause a form of nephronophthisis, an autosomal-recessive kidney disorder, in human patients. [provided by RefSeq, May 2017]

MAPKBP1 Gene-Disease associations (from GenCC):

• nephronophthisis 20

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• late-onset nephronophthisis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014994.3. 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
	MAPKBP1	NM_014994.3	MANE Select	c.207-155_207-144delAAAAAAAAAAAA		intron	N/A	NP_055809.2	O60336-6
	MAPKBP1	NM_001128608.2		c.207-155_207-144delAAAAAAAAAAAA		intron	N/A	NP_001122080.1	O60336-1
	MAPKBP1	NM_001265611.2		c.207-155_207-144delAAAAAAAAAAAA		intron	N/A	NP_001252540.1	O60336-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKBP1	ENST00000457542.7	TSL:1 MANE Select	c.207-155_207-144delAAAAAAAAAAAA		intron	N/A	ENSP00000397570.2	O60336-6
	MAPKBP1	ENST00000456763.6	TSL:1	c.207-155_207-144delAAAAAAAAAAAA		intron	N/A	ENSP00000393099.2	O60336-1
	MAPKBP1	ENST00000514566.5	TSL:1	c.207-155_207-144delAAAAAAAAAAAA		intron	N/A	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes AF: 0.0000119 AC: 1 AN: 84084 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000242

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000863 AC: 3 AN: 347806 Hom.: 0 AF XY: 0.0000109 AC XY: 2 AN XY: 183564

African (AFR) AF: 0.00 AC: 0 AN: 9926

American (AMR) AF: 0.00 AC: 0 AN: 13540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10422

East Asian (EAS) AF: 0.00 AC: 0 AN: 22104

South Asian (SAS) AF: 0.0000279 AC: 1 AN: 35886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1506

European-Non Finnish (NFE) AF: 0.00000957 AC: 2 AN: 209030

Other (OTH) AF: 0.00 AC: 0 AN: 19838

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000119 AC: 1 AN: 84084 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38870

African (AFR) AF: 0.00 AC: 0 AN: 23272

American (AMR) AF: 0.00 AC: 0 AN: 7712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2220

East Asian (EAS) AF: 0.00 AC: 0 AN: 2692

South Asian (SAS) AF: 0.00 AC: 0 AN: 2396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.0000242 AC: 1 AN: 41364

Other (OTH) AF: 0.00 AC: 0 AN: 1096

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs58612719; hg19: chr15-42102915;