Genetic Variant MAPKBP1:c.207-153_207-144delAAAAAAAAAA (chr15-41810717-CAAAAAAAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014994.3(MAPKBP1):c.207-153_207-144delAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000579 in 431,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000060 ( 0 hom. )

Consequence

MAPKBP1
NM_014994.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.625

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.207-153_207-144delAAAAAAAAAA	intron	N/A	NP_055809.2	O60336-6
MAPKBP1	NM_001128608.2		c.207-153_207-144delAAAAAAAAAA	intron	N/A	NP_001122080.1	O60336-1
MAPKBP1	NM_001265611.2		c.207-153_207-144delAAAAAAAAAA	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.207-153_207-144delAAAAAAAAAA	intron	N/A	ENSP00000397570.2	O60336-6
MAPKBP1	ENST00000456763.6	TSL:1	c.207-153_207-144delAAAAAAAAAA	intron	N/A	ENSP00000393099.2	O60336-1
MAPKBP1	ENST00000514566.5	TSL:1	c.207-153_207-144delAAAAAAAAAA	intron	N/A	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes

AF:

0.0000476

AC:

AN:

84084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000130

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:

0.0000484

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000604

AC:

AN:

347792

Hom.:

AF XY:

0.0000654

AC XY:

AN XY:

183556

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9924

American (AMR)

AF:

0.00

AC:

AN:

13540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10422

East Asian (EAS)

AF:

0.00

AC:

AN:

22104

South Asian (SAS)

AF:

0.0000279

AC:

AN:

35886

European-Finnish (FIN)

AF:

0.0000391

AC:

AN:

25552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1506

European-Non Finnish (NFE)

AF:

0.0000909

AC:

AN:

209020

Other (OTH)

AF:

0.00

AC:

AN:

19838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

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:

84072

Hom.:

Cov.:

AF XY:

0.0000772

AC XY:

AN XY:

38874

show subpopulations

African (AFR)

AF:

0.0000429

AC:

AN:

23312

American (AMR)

AF:

0.000130

AC:

AN:

7716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2220

East Asian (EAS)

AF:

0.00

AC:

AN:

2684

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:

0.0000484

AC:

AN:

41354

Other (OTH)

AF:

0.00

AC:

AN:

1104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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

0.63

Splicing

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

Publications

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15-41810717-CAAAAAAAAAAAAAAAA-CAAAAAA

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