rs17685379

Positions:

• chr17-45274682-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003954.5(MAP3K14):​c.1291-89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,476,580 control chromosomes in the GnomAD database, including 10,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (931 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10067 hom.)
• Consequence: MAP3K14 NM_003954.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305

Genes affected

MAP3K14 (HGNC:6853): (mitogen-activated protein kinase kinase kinase 14) This gene encodes mitogen-activated protein kinase kinase kinase 14, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-45274682-C-T is Benign according to our data. Variant chr17-45274682-C-T is described in ClinVar as [Benign]. Clinvar id is 2628305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.1291-89G>A		intron_variant		ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1	c.1291-89G>A		intron_variant			XP_047292953.1
MAP3K14	XM_047436998.1	c.1291-89G>A		intron_variant			XP_047292954.1
MAP3K14	XM_011525441.3	c.1291-89G>A		intron_variant			XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.1291-89G>A		intron_variant		1	NM_003954.5	ENSP00000478552.1
MAP3K14	ENST00000376926.8	c.1291-89G>A		intron_variant		1		ENSP00000482657.1
MAP3K14	ENST00000617331.3	c.1291-89G>A		intron_variant		5		ENSP00000480974.3
MAP3K14	ENST00000680632.1	n.139-89G>A		intron_variant				ENSP00000505027.1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15126 AN: 152086 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.121 AC: 159700 AN: 1324374 Hom.: 10067 AF XY: 0.119 AC XY: 77993 AN XY: 653320

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0927

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0636

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0994 AC: 15134 AN: 152206 Hom.: 931 Cov.: 32 AF XY: 0.0997 AC XY: 7419 AN XY: 74408

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.0874

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.109

Alfa AF: 0.108 Hom.: 171

Bravo AF: 0.0967

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.86
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17685379; hg19: chr17-43352049;