rs4792847

chr17-45306118-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+10842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,972 control chromosomes in the GnomAD database, including 21,990 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 0.53 (21990 hom., cov: 32)
• Consequence: MAP3K14 NM_003954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K14	NM_003954.5	c.-21+10842C>T		intron_variant		ENST00000344686.8
MAP3K14	XM_011525441.3	c.-21+6167C>T		intron_variant
MAP3K14	XM_047436997.1	c.-21+10842C>T		intron_variant
MAP3K14	XM_047436998.1	c.-21+6167C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K14	ENST00000344686.8	c.-21+10842C>T		intron_variant		1	NM_003954.5	P1
MAP3K14	ENST00000617331.3	c.-21+6167C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80351 AN: 151854 Hom.: 21941 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.529 AC: 80460 AN: 151972 Hom.: 21990 Cov.: 32 AF XY: 0.534 AC XY: 39706 AN XY: 74296

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.531

Alfa AF: 0.479 Hom.: 4915

Bravo AF: 0.544

Asia WGS AF: 0.689 AC: 2394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.1
Dann	Benign	0.66

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: rs4792847; hg19: chr17-43383484;