17-45299081-C-T

Variant names:

• chr17-45299081-C-T
• rs2867316
• NM_003954.5:c.-20-8316G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003954.5(MAP3K14):​c.-20-8316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,126 control chromosomes in the GnomAD database, including 8,573 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8573 hom., cov: 32)
• Consequence: MAP3K14 NM_003954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 21 publications found

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]

MAP3K14 Gene-Disease associations (from GenCC):

• NIK deficiency

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.-20-8316G>A		intron_variant	Intron 1 of 15	ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1	c.-20-8316G>A		intron_variant	Intron 1 of 14		XP_047292953.1
MAP3K14	XM_047436998.1	c.-20-8316G>A		intron_variant	Intron 2 of 15		XP_047292954.1
MAP3K14	XM_011525441.3	c.-20-8316G>A		intron_variant	Intron 2 of 16		XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.-20-8316G>A		intron_variant	Intron 1 of 15	1	NM_003954.5	ENSP00000478552.1
MAP3K14	ENST00000617331.3	c.-20-8316G>A		intron_variant	Intron 2 of 16	5		ENSP00000480974.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49496 AN: 152008 Hom.: 8562 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49543 AN: 152126 Hom.: 8573 Cov.: 32 AF XY: 0.330 AC XY: 24564 AN XY: 74374

African (AFR) AF: 0.264 AC: 10947 AN: 41474

American (AMR) AF: 0.430 AC: 6569 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1441 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3284 AN: 5172

South Asian (SAS) AF: 0.366 AC: 1765 AN: 4824

European-Finnish (FIN) AF: 0.301 AC: 3185 AN: 10594

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21169 AN: 67990

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.322 Hom.: 33231

Bravo AF: 0.333

Asia WGS AF: 0.466 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.65
PhyloP100		-0.86

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

Other links and lift over

dbSNP: rs2867316; hg19: chr17-43376447; COSMIC: COSV60924507;