15-41811358-C-T

Position:

• chr15-41811358-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014994.3(MAPKBP1):​c.327+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,030,254 control chromosomes in the GnomAD database, including 1,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (179 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1476 hom.)
• Consequence: MAPKBP1 NM_014994.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.847

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-41811358-C-T is Benign according to our data. Variant chr15-41811358-C-T is described in ClinVar as [Benign]. Clinvar id is 1297946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKBP1	NM_014994.3	c.327+123C>T		intron_variant		ENST00000457542.7	NP_055809.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKBP1	ENST00000457542.7	c.327+123C>T		intron_variant		1	NM_014994.3	ENSP00000397570	P4

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6011 AN: 152224 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0542 AC: 47581 AN: 877912 Hom.: 1476 Cov.: 12 AF XY: 0.0526 AC XY: 23944 AN XY: 455122

Gnomad4 AFR exome AF: 0.00928

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0200

Gnomad4 EAS exome AF: 0.000113

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.0728

Gnomad4 NFE exome AF: 0.0655

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.0394 AC: 6007 AN: 152342 Hom.: 179 Cov.: 32 AF XY: 0.0377 AC XY: 2811 AN XY: 74498

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0629

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0552 Hom.: 33

Bravo AF: 0.0349

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.57

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: rs77126542; hg19: chr15-42103556;