17-45290287-T-C

Variant names:

• chr17-45290287-T-C
• rs7222094
• NM_003954.5:c.256+203A>G

Variant summary

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

The NM_003954.5(MAP3K14):​c.256+203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,078 control chromosomes in the GnomAD database, including 23,377 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 0.54 (23377 hom., cov: 32)
• Consequence: MAP3K14 NM_003954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.256+203A>G		intron_variant	Intron 2 of 15	ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1	c.256+203A>G		intron_variant	Intron 2 of 14		XP_047292953.1
MAP3K14	XM_047436998.1	c.256+203A>G		intron_variant	Intron 3 of 15		XP_047292954.1
MAP3K14	XM_011525441.3	c.256+203A>G		intron_variant	Intron 3 of 16		XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.256+203A>G		intron_variant	Intron 2 of 15	1	NM_003954.5	ENSP00000478552.1
MAP3K14	ENST00000376926.8	c.256+203A>G		intron_variant	Intron 1 of 14	1		ENSP00000482657.1
MAP3K14	ENST00000617331.3	c.256+203A>G		intron_variant	Intron 3 of 16	5		ENSP00000480974.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82718 AN: 151960 Hom.: 23331 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.545 AC: 82821 AN: 152078 Hom.: 23377 Cov.: 32 AF XY: 0.550 AC XY: 40866 AN XY: 74346

African (AFR) AF: 0.594 AC: 24628 AN: 41468

American (AMR) AF: 0.688 AC: 10525 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3468

East Asian (EAS) AF: 0.883 AC: 4557 AN: 5158

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4818

European-Finnish (FIN) AF: 0.506 AC: 5352 AN: 10586

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31738 AN: 67976

Other (OTH) AF: 0.563 AC: 1187 AN: 2110

Alfa AF: 0.527 Hom.: 11208

Bravo AF: 0.562

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.52
PhyloP100		-1.7

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: rs7222094; hg19: chr17-43367653;