rs7216796

Positions:

• chr17-45314842-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.-21+2118C>T		intron_variant		ENST00000344686.8	NP_003945.2
MAP3K14	XM_011525441.3	c.-174+2118C>T		intron_variant			XP_011523743.1
MAP3K14	XM_047436997.1	c.-21+2118C>T		intron_variant			XP_047292953.1
MAP3K14	XM_047436998.1	c.-174+2118C>T		intron_variant			XP_047292954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.-21+2118C>T		intron_variant		1	NM_003954.5	ENSP00000478552	P1
MAP3K14	ENST00000617331.3	c.-174+2118C>T		intron_variant		5		ENSP00000480974	P1

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

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.477

Alfa AF: 0.518 Hom.: 19440

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7216796; hg19: chr17-43392208;