15-41810717-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant names:

• chr15-41810717-CA-C
• rs58612719
• NM_014994.3:c.207-144delA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014994.3(MAPKBP1):​c.207-144delA 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 0.016 (19 hom., cov: 0)
  • Exomes 𝑓: 0.11 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKBP1 NM_014994.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 1364 AN: 83818 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00377

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00631

Gnomad EAS AF: 0.00892

Gnomad SAS AF: 0.00710

Gnomad FIN AF: 0.000761

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.0128

GnomAD4 exome AF: 0.110 AC: 37680 AN: 341162 Hom.: 3 Cov.: 0 AF XY: 0.111 AC XY: 19985 AN XY: 180066

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

African (AFR) AF: 0.101 AC: 979 AN: 9646

American (AMR) AF: 0.110 AC: 1456 AN: 13266

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 1200 AN: 10244

East Asian (EAS) AF: 0.154 AC: 3357 AN: 21746

South Asian (SAS) AF: 0.0932 AC: 3276 AN: 35160

European-Finnish (FIN) AF: 0.0968 AC: 2431 AN: 25120

Middle Eastern (MID) AF: 0.100 AC: 146 AN: 1458

European-Non Finnish (NFE) AF: 0.110 AC: 22593 AN: 205038

Other (OTH) AF: 0.115 AC: 2242 AN: 19484

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0163 AC: 1366 AN: 83806 Hom.: 19 Cov.: 0 AF XY: 0.0164 AC XY: 637 AN XY: 38760

African (AFR) AF: 0.0453 AC: 1053 AN: 23268

American (AMR) AF: 0.0101 AC: 78 AN: 7710

Ashkenazi Jewish (ASJ) AF: 0.00631 AC: 14 AN: 2218

East Asian (EAS) AF: 0.00895 AC: 24 AN: 2682

South Asian (SAS) AF: 0.00633 AC: 15 AN: 2368

European-Finnish (FIN) AF: 0.000761 AC: 2 AN: 2628

Middle Eastern (MID) AF: 0.0195 AC: 3 AN: 154

European-Non Finnish (NFE) AF: 0.00391 AC: 161 AN: 41146

Other (OTH) AF: 0.0127 AC: 14 AN: 1102

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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;