rs303426

Positions:

• chr10-30451450-G-A
• chr10-30451450-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005204.4(MAP3K8):​c.767-188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,014 control chromosomes in the GnomAD database, including 21,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (21672 hom., cov: 32)
• Consequence: MAP3K8 NM_005204.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.409

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-30451450-G-A is Benign according to our data. Variant chr10-30451450-G-A is described in ClinVar as [Benign]. Clinvar id is 1262218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K8	NM_005204.4	c.767-188G>A		intron_variant		ENST00000263056.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K8	ENST00000263056.6	c.767-188G>A		intron_variant		1	NM_005204.4	P1
MAP3K8	ENST00000375321.1	c.767-188G>A		intron_variant		1		P1
MAP3K8	ENST00000542547.5	c.767-188G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74867 AN: 151896 Hom.: 21679 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.493 AC: 74870 AN: 152014 Hom.: 21672 Cov.: 32 AF XY: 0.489 AC XY: 36332 AN XY: 74284

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.516

Alfa AF: 0.569 Hom.: 4049

Bravo AF: 0.473

Asia WGS AF: 0.382 AC: 1327 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.16

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: rs303426; hg19: chr10-30740379;