15-41810717-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr15-41810717-CAA-C
• rs58612719
• NM_014994.3:c.207-145_207-144delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014994.3(MAPKBP1):​c.207-145_207-144delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 342,536 control chromosomes in the GnomAD database, including 379 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (20169 hom., cov: 0)
  • Exomes 𝑓: 0.37 (379 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKBP1 NM_014994.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.616
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-41810717-CAA-C is Benign according to our data. Variant chr15-41810717-CAA-C is described in ClinVar as Benign. ClinVar VariationId is 1284119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

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.207-145_207-144delAA		intron	N/A	NP_055809.2	O60336-6
	MAPKBP1	NM_001128608.2		c.207-145_207-144delAA		intron	N/A	NP_001122080.1	O60336-1
	MAPKBP1	NM_001265611.2		c.207-145_207-144delAA		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.207-145_207-144delAA		intron	N/A	ENSP00000397570.2	O60336-6
	MAPKBP1	ENST00000456763.6	TSL:1	c.207-145_207-144delAA		intron	N/A	ENSP00000393099.2	O60336-1
	MAPKBP1	ENST00000514566.5	TSL:1	c.207-145_207-144delAA		intron	N/A	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes AF: 0.715 AC: 59645 AN: 83472 Hom.: 20180 Cov.: 0

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.855

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.373 AC: 127832 AN: 342536 Hom.: 379 AF XY: 0.373 AC XY: 67351 AN XY: 180790

African (AFR) AF: 0.353 AC: 3312 AN: 9382

American (AMR) AF: 0.364 AC: 4825 AN: 13260

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 4062 AN: 10312

East Asian (EAS) AF: 0.216 AC: 4596 AN: 21260

South Asian (SAS) AF: 0.368 AC: 12981 AN: 35260

European-Finnish (FIN) AF: 0.369 AC: 9347 AN: 25358

Middle Eastern (MID) AF: 0.408 AC: 605 AN: 1484

European-Non Finnish (NFE) AF: 0.390 AC: 80625 AN: 206708

Other (OTH) AF: 0.383 AC: 7479 AN: 19512

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.714 AC: 59632 AN: 83462 Hom.: 20169 Cov.: 0 AF XY: 0.714 AC XY: 27553 AN XY: 38578

African (AFR) AF: 0.634 AC: 14624 AN: 23050

American (AMR) AF: 0.720 AC: 5524 AN: 7674

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 1689 AN: 2194

East Asian (EAS) AF: 0.373 AC: 992 AN: 2660

South Asian (SAS) AF: 0.774 AC: 1811 AN: 2340

European-Finnish (FIN) AF: 0.839 AC: 2199 AN: 2620

Middle Eastern (MID) AF: 0.849 AC: 129 AN: 152

European-Non Finnish (NFE) AF: 0.765 AC: 31464 AN: 41152

Other (OTH) AF: 0.693 AC: 755 AN: 1090

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs58612719; hg19: chr15-42102915;