NM_014994.3:c.207-149_207-144delAAAAAA

Variant names:

• chr15-41810717-CAAAAAA-C
• rs58612719
• NM_014994.3:c.207-149_207-144delAAAAAA

Variant summary

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

The NM_014994.3(MAPKBP1):​c.207-149_207-144delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 424,982 control chromosomes in the GnomAD database, including 281 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (280 hom., cov: 0)
  • Exomes 𝑓: 0.013 (1 hom.)
• 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-CAAAAAA-C is Benign according to our data. Variant chr15-41810717-CAAAAAA-C is described in ClinVar as Benign. ClinVar VariationId is 1282069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 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.207-149_207-144delAAAAAA		intron	N/A	NP_055809.2	O60336-6
	MAPKBP1	NM_001128608.2		c.207-149_207-144delAAAAAA		intron	N/A	NP_001122080.1	O60336-1
	MAPKBP1	NM_001265611.2		c.207-149_207-144delAAAAAA		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.207-149_207-144delAAAAAA		intron	N/A	ENSP00000397570.2	O60336-6
	MAPKBP1	ENST00000456763.6	TSL:1	c.207-149_207-144delAAAAAA		intron	N/A	ENSP00000393099.2	O60336-1
	MAPKBP1	ENST00000514566.5	TSL:1	c.207-149_207-144delAAAAAA		intron	N/A	ENSP00000426154.1	O60336-2

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 4388 AN: 84084 Hom.: 279 Cov.: 0

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.000381

Gnomad MID AF: 0.00575

Gnomad NFE AF: 0.000363

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.0132 AC: 4494 AN: 340910 Hom.: 1 AF XY: 0.0127 AC XY: 2287 AN XY: 179918

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

African (AFR) AF: 0.117 AC: 1132 AN: 9686

American (AMR) AF: 0.0145 AC: 192 AN: 13270

Ashkenazi Jewish (ASJ) AF: 0.00911 AC: 93 AN: 10212

East Asian (EAS) AF: 0.00264 AC: 58 AN: 21996

South Asian (SAS) AF: 0.0101 AC: 355 AN: 35092

European-Finnish (FIN) AF: 0.00972 AC: 244 AN: 25102

Middle Eastern (MID) AF: 0.0121 AC: 18 AN: 1486

European-Non Finnish (NFE) AF: 0.0101 AC: 2068 AN: 204630

Other (OTH) AF: 0.0172 AC: 334 AN: 19436

⚠️ 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: 0.0522 AC: 4392 AN: 84072 Hom.: 280 Cov.: 0 AF XY: 0.0530 AC XY: 2060 AN XY: 38870

African (AFR) AF: 0.179 AC: 4170 AN: 23316

American (AMR) AF: 0.0207 AC: 160 AN: 7714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2220

East Asian (EAS) AF: 0.00 AC: 0 AN: 2684

South Asian (SAS) AF: 0.000844 AC: 2 AN: 2370

European-Finnish (FIN) AF: 0.000381 AC: 1 AN: 2628

Middle Eastern (MID) AF: 0.00649 AC: 1 AN: 154

European-Non Finnish (NFE) AF: 0.000363 AC: 15 AN: 41352

Other (OTH) AF: 0.0389 AC: 43 AN: 1104

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

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

Other links and lift over

dbSNP: rs58612719; hg19: chr15-42102915;