6-90581815-A-G

Variant names:

• chr6-90581815-A-G
• rs3799897
• NM_145331.3:c.120+4949T>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.120+4949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,102 control chromosomes in the GnomAD database, including 4,064 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 0.21 (4064 hom., cov: 32)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• 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: 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7	NM_145331.3	MANE Select	c.120+4949T>C		intron	N/A	NP_663304.1
	MAP3K7	NM_003188.4		c.120+4949T>C		intron	N/A	NP_003179.1
	MAP3K7	NM_145332.3		c.120+4949T>C		intron	N/A	NP_663305.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7	ENST00000369329.8	TSL:1 MANE Select	c.120+4949T>C		intron	N/A	ENSP00000358335.3
	MAP3K7	ENST00000369332.7	TSL:1	c.120+4949T>C		intron	N/A	ENSP00000358338.3
	MAP3K7	ENST00000369325.7	TSL:1	c.120+4949T>C		intron	N/A	ENSP00000358331.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32699 AN: 151984 Hom.: 4066 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.215 AC: 32691 AN: 152102 Hom.: 4064 Cov.: 32 AF XY: 0.214 AC XY: 15901 AN XY: 74368

African (AFR) AF: 0.106 AC: 4407 AN: 41512

American (AMR) AF: 0.169 AC: 2577 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 858 AN: 3466

East Asian (EAS) AF: 0.0977 AC: 505 AN: 5170

South Asian (SAS) AF: 0.134 AC: 647 AN: 4832

European-Finnish (FIN) AF: 0.323 AC: 3411 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19506 AN: 67966

Other (OTH) AF: 0.222 AC: 467 AN: 2106

Alfa AF: 0.212 Hom.: 2589

Bravo AF: 0.200

Asia WGS AF: 0.152 AC: 527 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		2.2
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: rs3799897; hg19: chr6-91291534; COSMIC: COSV65235330;