6-90551148-T-C

Position:

• chr6-90551148-T-C

Variant summary

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

The NM_145331.3(MAP3K7):​c.868-599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,026 control chromosomes in the GnomAD database, including 33,174 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 0.66 (33162 hom., cov: 32)
  • Exomes 𝑓: 0.59 (12 hom.)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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]

MAP3K7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.868-599A>G		intron_variant		ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.868-599A>G		intron_variant		1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99896 AN: 151838 Hom.: 33147 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.586 AC: 41 AN: 70 Hom.: 12 Cov.: 0 AF XY: 0.667 AC XY: 28 AN XY: 42

Gnomad4 AMR exome AF: 0.375

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.658 AC: 99953 AN: 151956 Hom.: 33162 Cov.: 32 AF XY: 0.653 AC XY: 48480 AN XY: 74266

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.694

Alfa AF: 0.677 Hom.: 33929

Bravo AF: 0.653

Asia WGS AF: 0.573 AC: 1988 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.032
DANN	Benign	0.53

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: rs157688; hg19: chr6-91260867;