rs7216796

Variant names:

• chr17-45314842-G-A
• rs7216796
• NM_003954.5:c.-21+2118C>T

Variant summary

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

The NM_003954.5(MAP3K14):​c.-21+2118C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,818 control chromosomes in the GnomAD database, including 18,510 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 0.49 (18510 hom., cov: 30)
• Consequence: MAP3K14 NM_003954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771
• Publications: 11 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.-21+2118C>T		intron_variant	Intron 1 of 15	ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1	c.-21+2118C>T		intron_variant	Intron 1 of 14		XP_047292953.1
MAP3K14	XM_047436998.1	c.-174+2118C>T		intron_variant	Intron 1 of 15		XP_047292954.1
MAP3K14	XM_011525441.3	c.-174+2118C>T		intron_variant	Intron 1 of 16		XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.-21+2118C>T		intron_variant	Intron 1 of 15	1	NM_003954.5	ENSP00000478552.1
MAP3K14	ENST00000617331.3	c.-174+2118C>T		intron_variant	Intron 1 of 16	5		ENSP00000480974.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73647 AN: 151700 Hom.: 18504 Cov.: 30

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.485 AC: 73660 AN: 151818 Hom.: 18510 Cov.: 30 AF XY: 0.479 AC XY: 35506 AN XY: 74172

African (AFR) AF: 0.498 AC: 20589 AN: 41340

American (AMR) AF: 0.346 AC: 5282 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3468

East Asian (EAS) AF: 0.123 AC: 636 AN: 5170

South Asian (SAS) AF: 0.528 AC: 2545 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5007 AN: 10522

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36366 AN: 67942

Other (OTH) AF: 0.477 AC: 1004 AN: 2106

Alfa AF: 0.514 Hom.: 28768

Bravo AF: 0.476

Asia WGS AF: 0.303 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		0.77

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: rs7216796; hg19: chr17-43392208;