rs306588

Positions:

• chr10-30434664-G-A
• chr10-30434664-G-T

Variant summary

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

The NM_005204.4(MAP3K8):​c.-255+286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 985,396 control chromosomes in the GnomAD database, including 240,782 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 0.71 (39247 hom., cov: 34)
  • Exomes 𝑓: 0.69 (201535 hom.)
• Consequence: MAP3K8 NM_005204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K8	NM_005204.4	c.-255+286G>A		intron_variant		ENST00000263056.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K8	ENST00000263056.6	c.-255+286G>A		intron_variant		1	NM_005204.4	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108443 AN: 152048 Hom.: 39207 Cov.: 34

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.694 AC: 578237 AN: 833230 Hom.: 201535 Cov.: 45 AF XY: 0.693 AC XY: 266717 AN XY: 384794

Gnomad4 AFR exome AF: 0.805

Gnomad4 AMR exome AF: 0.733

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.713 AC: 108540 AN: 152166 Hom.: 39247 Cov.: 34 AF XY: 0.706 AC XY: 52548 AN XY: 74386

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.715

Alfa AF: 0.717 Hom.: 5368

Bravo AF: 0.722

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs306588; hg19: chr10-30723593;