rs303450

Positions:

• chr10-30436408-C-A
• chr10-30436408-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005204.4(MAP3K8):​c.-254-768C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 151,978 control chromosomes in the GnomAD database, including 41,168 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 0.73 (41168 hom., cov: 30)
• Consequence: MAP3K8 NM_005204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

MAP3K8 (HGNC:6860): (mitogen-activated protein kinase kinase kinase 8) This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K8	NM_005204.4	c.-254-768C>A		intron_variant		ENST00000263056.6	NP_005195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K8	ENST00000263056.6	c.-254-768C>A		intron_variant		1	NM_005204.4	ENSP00000263056.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110725 AN: 151860 Hom.: 41116 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.729 AC: 110837 AN: 151978 Hom.: 41168 Cov.: 30 AF XY: 0.722 AC XY: 53636 AN XY: 74266

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.728

Alfa AF: 0.732 Hom.: 5735

Bravo AF: 0.741

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.27
DANN	Benign	0.84

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: rs303450; hg19: chr10-30725337;