chr6-90543867-A-G

Variant names:

• chr6-90543867-A-G
• rs967779
• NM_145331.3:c.1291+685T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145331.3(MAP3K7):​c.1291+685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,010 control chromosomes in the GnomAD database, including 5,937 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 0.27 (5937 hom., cov: 32)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 3 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• frontometaphyseal dysplasia

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145331.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7	NM_145331.3	MANE Select	c.1291+685T>C		intron	N/A	NP_663304.1	O43318-1
	MAP3K7	NM_003188.4		c.1210+3391T>C		intron	N/A	NP_003179.1	O43318-2
	MAP3K7	NM_145332.3		c.1291+685T>C		intron	N/A	NP_663305.1	O43318-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7	ENST00000369329.8	TSL:1 MANE Select	c.1291+685T>C		intron	N/A	ENSP00000358335.3	O43318-1
	MAP3K7	ENST00000369332.7	TSL:1	c.1210+3391T>C		intron	N/A	ENSP00000358338.3	O43318-2
	MAP3K7	ENST00000369325.7	TSL:1	c.1291+685T>C		intron	N/A	ENSP00000358331.3	O43318-3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40536 AN: 151892 Hom.: 5934 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.267 AC: 40558 AN: 152010 Hom.: 5937 Cov.: 32 AF XY: 0.265 AC XY: 19714 AN XY: 74304

African (AFR) AF: 0.141 AC: 5840 AN: 41518

American (AMR) AF: 0.304 AC: 4638 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1594 AN: 3460

East Asian (EAS) AF: 0.312 AC: 1604 AN: 5148

South Asian (SAS) AF: 0.422 AC: 2037 AN: 4826

European-Finnish (FIN) AF: 0.239 AC: 2526 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21281 AN: 67928

Other (OTH) AF: 0.313 AC: 660 AN: 2112

Alfa AF: 0.277 Hom.: 1914

Bravo AF: 0.262

Asia WGS AF: 0.335 AC: 1166 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.55
DANN	Benign	0.81
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism (auto)

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: rs967779; hg19: chr6-91253586; COSMIC: COSV65223942;