rs157705

Positions:

• chr6-90515416-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.*1085G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,652 control chromosomes in the GnomAD database, including 10,033 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 0.36 (10033 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MAP3K7 NM_145331.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7	NM_145331.3	c.*1085G>A		3_prime_UTR_variant	17/17	ENST00000369329.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7	ENST00000369329.8	c.*1085G>A		3_prime_UTR_variant	17/17	1	NM_145331.3	P3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54134 AN: 151534 Hom.: 10024 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.380

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.357 AC: 54190 AN: 151652 Hom.: 10033 Cov.: 32 AF XY: 0.353 AC XY: 26168 AN XY: 74152

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.385

Alfa AF: 0.332 Hom.: 10071

Bravo AF: 0.365

Asia WGS AF: 0.355 AC: 1235 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.71

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: rs157705; hg19: chr6-91225135;