17-45281051-T-C

Variant names:

• chr17-45281051-T-C
• rs16939948
• NM_003954.5:c.1290+3761A>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.1290+3761A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 152,218 control chromosomes in the GnomAD database, including 172 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 0.038 (172 hom., cov: 31)
• Consequence: MAP3K14 NM_003954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.1290+3761A>G		intron_variant	Intron 6 of 15	ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1	c.1290+3761A>G		intron_variant	Intron 6 of 14		XP_047292953.1
MAP3K14	XM_047436998.1	c.1290+3761A>G		intron_variant	Intron 7 of 15		XP_047292954.1
MAP3K14	XM_011525441.3	c.1290+3761A>G		intron_variant	Intron 7 of 16		XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.1290+3761A>G		intron_variant	Intron 6 of 15	1	NM_003954.5	ENSP00000478552.1
MAP3K14	ENST00000376926.8	c.1290+3761A>G		intron_variant	Intron 5 of 14	1		ENSP00000482657.1
MAP3K14	ENST00000617331.3	c.1290+3761A>G		intron_variant	Intron 7 of 16	5		ENSP00000480974.3
MAP3K14	ENST00000680632.1	n.138+3761A>G		intron_variant	Intron 1 of 10			ENSP00000505027.1

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5844 AN: 152100 Hom.: 173 Cov.: 31

Gnomad AFR AF: 0.00954

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0384 AC: 5843 AN: 152218 Hom.: 172 Cov.: 31 AF XY: 0.0406 AC XY: 3022 AN XY: 74430

African (AFR) AF: 0.00951 AC: 395 AN: 41538

American (AMR) AF: 0.0355 AC: 542 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3466

East Asian (EAS) AF: 0.112 AC: 578 AN: 5174

South Asian (SAS) AF: 0.0815 AC: 393 AN: 4822

European-Finnish (FIN) AF: 0.0597 AC: 633 AN: 10600

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2976 AN: 68016

Other (OTH) AF: 0.0421 AC: 89 AN: 2112

Alfa AF: 0.0193 Hom.: 14

Bravo AF: 0.0362

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.58
PhyloP100		-0.39

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: rs16939948; hg19: chr17-43358418;