rs2131906

Variant names:

• chr6-90516323-T-C
• rs2131906
• NM_145331.3:c.*178A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• cardiospondylocarpofacial syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• frontometaphyseal dysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina
• frontometaphyseal dysplasia 2

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.*178A>G		3_prime_UTR_variant	Exon 17 of 17	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.*178A>G		3_prime_UTR_variant	Exon 17 of 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

African (AFR) AF: 0.0189 AC: 240 AN: 12680

American (AMR) AF: 0.0291 AC: 524 AN: 17980

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 497 AN: 14356

East Asian (EAS) AF: 0.0253 AC: 786 AN: 31018

South Asian (SAS) AF: 0.0500 AC: 2321 AN: 46406

European-Finnish (FIN) AF: 0.00797 AC: 281 AN: 35238

Middle Eastern (MID) AF: 0.0535 AC: 109 AN: 2036

European-Non Finnish (NFE) AF: 0.0318 AC: 9711 AN: 305014

Other (OTH) AF: 0.0367 AC: 996 AN: 27162

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

African (AFR) AF: 0.0190 AC: 789 AN: 41448

American (AMR) AF: 0.0375 AC: 571 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.0347 AC: 179 AN: 5160

South Asian (SAS) AF: 0.0438 AC: 211 AN: 4812

European-Finnish (FIN) AF: 0.00728 AC: 77 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2047 AN: 67908

Other (OTH) AF: 0.0389 AC: 82 AN: 2108

Alfa AF: 0.0294 Hom.: 51

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
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2131906; hg19: chr6-91226042;