rs282070

Positions:

• chr6-90586701-C-G

Variant summary

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

The NM_145331.3(MAP3K7):​c.120+63G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,537,468 control chromosomes in the GnomAD database, including 372,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36428 hom., cov: 34)
  • Exomes 𝑓: 0.69 (336569 hom.)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840

Genes affected

MAP3K7 (HGNC:6859): (mitogen-activated protein kinase kinase kinase 7) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-90586701-C-G is Benign according to our data. Variant chr6-90586701-C-G is described in ClinVar as [Benign]. Clinvar id is 1241619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.120+63G>C		intron_variant		ENST00000369329.8	NP_663304.1
MAP3K7	NM_003188.4	c.120+63G>C		intron_variant			NP_003179.1
MAP3K7	NM_145332.3	c.120+63G>C		intron_variant			NP_663305.1
MAP3K7	NM_145333.3	c.120+63G>C		intron_variant			NP_663306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.120+63G>C		intron_variant		1	NM_145331.3	ENSP00000358335	P3

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104822 AN: 152040 Hom.: 36403 Cov.: 34

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.695 AC: 962733 AN: 1385310 Hom.: 336569 AF XY: 0.697 AC XY: 476635 AN XY: 683666

Gnomad4 AFR exome AF: 0.717

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.644

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.689 AC: 104893 AN: 152158 Hom.: 36428 Cov.: 34 AF XY: 0.684 AC XY: 50851 AN XY: 74380

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.738

Alfa AF: 0.698 Hom.: 4616

Bravo AF: 0.687

Asia WGS AF: 0.637 AC: 2217 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.51

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: rs282070; hg19: chr6-91296420; COSMIC: COSV65235341;