NM_014994.3:c.207-144dupA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_014994.3(MAPKBP1):​c.207-144dupA 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 0.00063 (0 hom., cov: 0)
  • Exomes 𝑓: 0.012 (0 hom.)
• 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.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000631 (53/84048) while in subpopulation EAS AF = 0.00299 (8/2674). AF 95% confidence interval is 0.00149. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 53 AN: 84060 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000860

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000389

Gnomad ASJ AF: 0.000450

Gnomad EAS AF: 0.00298

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000484

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0118 AC: 4090 AN: 346044 Hom.: 0 Cov.: 0 AF XY: 0.0117 AC XY: 2137 AN XY: 182682

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

African (AFR) AF: 0.00476 AC: 47 AN: 9884

American (AMR) AF: 0.0128 AC: 172 AN: 13434

Ashkenazi Jewish (ASJ) AF: 0.00887 AC: 92 AN: 10374

East Asian (EAS) AF: 0.0578 AC: 1262 AN: 21850

South Asian (SAS) AF: 0.00983 AC: 351 AN: 35694

European-Finnish (FIN) AF: 0.00648 AC: 165 AN: 25446

Middle Eastern (MID) AF: 0.00600 AC: 9 AN: 1500

European-Non Finnish (NFE) AF: 0.00860 AC: 1789 AN: 208108

Other (OTH) AF: 0.0103 AC: 203 AN: 19754

⚠️ 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 AF: 0.000631 AC: 53 AN: 84048 Hom.: 0 Cov.: 0 AF XY: 0.000592 AC XY: 23 AN XY: 38862

African (AFR) AF: 0.000858 AC: 20 AN: 23306

American (AMR) AF: 0.000389 AC: 3 AN: 7714

Ashkenazi Jewish (ASJ) AF: 0.000450 AC: 1 AN: 2220

East Asian (EAS) AF: 0.00299 AC: 8 AN: 2674

South Asian (SAS) AF: 0.000422 AC: 1 AN: 2370

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.000484 AC: 20 AN: 41348

Other (OTH) AF: 0.00 AC: 0 AN: 1104

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58612719; hg19: chr15-42102915;