Genetic Variant MAPKBP1:c.207-145_207-144dupAA (chr15-41810717-C-CAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014994.3(MAPKBP1):c.207-145_207-144dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

MAPKBP1
NM_014994.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.616

Publications

0 publications found

Variant links:

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

MAPKBP1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAPKBP1	NM_014994.3	MANE Select	c.207-145_207-144dupAA	intron	N/A	NP_055809.2	O60336-6
MAPKBP1	NM_001128608.2		c.207-145_207-144dupAA	intron	N/A	NP_001122080.1	O60336-1
MAPKBP1	NM_001265611.2		c.207-145_207-144dupAA	intron	N/A	NP_001252540.1	O60336-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAPKBP1	ENST00000457542.7	TSL:1 MANE Select	c.207-145_207-144dupAA	intron	N/A	ENSP00000397570.2	O60336-6
MAPKBP1	ENST00000456763.6	TSL:1	c.207-145_207-144dupAA	intron	N/A	ENSP00000393099.2	O60336-1
MAPKBP1	ENST00000514566.5	TSL:1	c.207-145_207-144dupAA	intron	N/A	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes

AF:

0.0000476

AC:

AN:

84074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000859

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000743

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00109

AC:

377

AN:

347254

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

199

AN XY:

183280

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000504

AC:

AN:

9918

American (AMR)

AF:

0.00111

AC:

AN:

13514

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

10404

East Asian (EAS)

AF:

0.00619

AC:

136

AN:

21972

South Asian (SAS)

AF:

0.000977

AC:

AN:

35838

European-Finnish (FIN)

AF:

0.000548

AC:

AN:

25526

Middle Eastern (MID)

AF:

0.00133

AC:

AN:

1506

European-Non Finnish (NFE)

AF:

0.000671

AC:

140

AN:

208772

Other (OTH)

AF:

0.00121

AC:

AN:

19804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.259

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000476

AC:

AN:

84062

Hom.:

Cov.:

AF XY:

0.0000257

AC XY:

AN XY:

38872

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000858

AC:

AN:

23312

American (AMR)

AF:

0.00

AC:

AN:

7716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2220

East Asian (EAS)

AF:

0.000746

AC:

AN:

2682

South Asian (SAS)

AF:

0.00

AC:

AN:

2370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

154

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41346

Other (OTH)

AF:

0.00

AC:

AN:

1104

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0409185), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

Splicing

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

Publications

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15-41810717-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over