15-41810717-CAAAAAA-C

Position:

• chr15-41810717-CAAAAAA-C

Variant summary

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

The NM_014994.3(MAPKBP1):​c.207-149_207-144del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 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

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-CAAAAAA-C is Benign according to our data. Variant chr15-41810717-CAAAAAA-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKBP1	NM_014994.3	c.207-149_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.207-149_207-144del		intron_variant		1	NM_014994.3	ENSP00000397570	P4

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

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.00911

Gnomad4 EAS exome AF: 0.00264

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00972

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0522 AC: 4392 AN: 84072 Hom.: 280 Cov.: 0 AF XY: 0.0530 AC XY: 2060 AN XY: 38870

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000844

Gnomad4 FIN AF: 0.000381

Gnomad4 NFE AF: 0.000363

Gnomad4 OTH AF: 0.0389

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 24, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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;