6-90568949-C-T

Position:

• chr6-90568949-C-T

Variant summary

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

The NM_145331.3(MAP3K7):​c.232-326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,952 control chromosomes in the GnomAD database, including 4,359 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 0.23 (4359 hom., cov: 31)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7	NM_145331.3	c.232-326G>A		intron_variant		ENST00000369329.8
MAP3K7	NM_003188.4	c.232-326G>A		intron_variant
MAP3K7	NM_145332.3	c.232-326G>A		intron_variant
MAP3K7	NM_145333.3	c.232-326G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7	ENST00000369329.8	c.232-326G>A		intron_variant		1	NM_145331.3	P3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34933 AN: 151834 Hom.: 4361 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.230 AC: 34925 AN: 151952 Hom.: 4359 Cov.: 31 AF XY: 0.229 AC XY: 16999 AN XY: 74276

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0986

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.230

Alfa AF: 0.266 Hom.: 5376

Bravo AF: 0.217

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.78

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: rs1145736; hg19: chr6-91278668; COSMIC: COSV65235316;