rs2131906

Positions:

• chr6-90516323-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145331.3(MAP3K7):​c.*178A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 643,796 control chromosomes in the GnomAD database, including 397 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 0.027 (69 hom., cov: 32)
  • Exomes 𝑓: 0.031 (328 hom.)
• Consequence: MAP3K7 NM_145331.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.027 (4100/151906) while in subpopulation SAS AF= 0.0438 (211/4812). AF 95% confidence interval is 0.039. There are 69 homozygotes in gnomad4. There are 1994 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.*178A>G		3_prime_UTR_variant	17/17	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329	c.*178A>G		3_prime_UTR_variant	17/17	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4096 AN: 151788 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0438

Gnomad FIN AF: 0.00728

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0393

GnomAD4 exome AF: 0.0314 AC: 15465 AN: 491890 Hom.: 328 Cov.: 6 AF XY: 0.0328 AC XY: 8552 AN XY: 260856

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0346

Gnomad4 EAS exome AF: 0.0253

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.00797

Gnomad4 NFE exome AF: 0.0318

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0270 AC: 4100 AN: 151906 Hom.: 69 Cov.: 32 AF XY: 0.0269 AC XY: 1994 AN XY: 74256

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.0438

Gnomad4 FIN AF: 0.00728

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0289 Hom.: 40

Bravo AF: 0.0296

Asia WGS AF: 0.0530 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0070
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2131906; hg19: chr6-91226042;