15-41810717-CAA-C

Position:

• chr15-41810717-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014994.3(MAPKBP1):​c.207-145_207-144del 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKBP1	NM_014994.3	c.207-145_207-144del		intron_variant		ENST00000457542.7	NP_055809.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKBP1	ENST00000457542.7	c.207-145_207-144del		intron_variant		1	NM_014994.3	ENSP00000397570	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 59645 AN: 83472 Hom.: 20180 Cov.: 0 FAILED QC

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

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.383

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

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.693

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs58612719; hg19: chr15-42102915;