rs303426

Variant names:

• chr10-30451450-G-A
• rs303426
• NM_005204.4:c.767-188G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K8	NM_005204.4	MANE Select	c.767-188G>A		intron	N/A	NP_005195.2
	MAP3K8	NM_001244134.1		c.767-188G>A		intron	N/A	NP_001231063.1
	MAP3K8	NM_001320961.2		c.767-188G>A		intron	N/A	NP_001307890.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K8	ENST00000263056.6	TSL:1 MANE Select	c.767-188G>A		intron	N/A	ENSP00000263056.1
	MAP3K8	ENST00000375321.1	TSL:1	c.767-188G>A		intron	N/A	ENSP00000364470.1
	MAP3K8	ENST00000542547.5	TSL:1	c.767-188G>A		intron	N/A	ENSP00000443610.1

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

African (AFR) AF: 0.183 AC: 7604 AN: 41480

American (AMR) AF: 0.556 AC: 8494 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2070 AN: 5160

South Asian (SAS) AF: 0.360 AC: 1732 AN: 4816

European-Finnish (FIN) AF: 0.628 AC: 6621 AN: 10548

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.655 AC: 44520 AN: 67948

Other (OTH) AF: 0.516 AC: 1087 AN: 2106

Alfa AF: 0.556 Hom.: 4065

Bravo AF: 0.473

Asia WGS AF: 0.382 AC: 1327 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.16
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs303426; hg19: chr10-30740379;