6-90579084-G-C

Variant names:

• chr6-90579084-G-C
• rs16883216
• NM_145331.3:c.121-7277C>G

Variant summary

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

The NM_145331.3(MAP3K7):​c.121-7277C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 152,202 control chromosomes in the GnomAD database, including 303 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 0.050 (303 hom., cov: 32)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 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.121-7277C>G		intron	N/A	NP_663304.1
	MAP3K7	NM_003188.4		c.121-7277C>G		intron	N/A	NP_003179.1
	MAP3K7	NM_145332.3		c.121-7277C>G		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.121-7277C>G		intron	N/A	ENSP00000358335.3
	MAP3K7	ENST00000369332.7	TSL:1	c.121-7277C>G		intron	N/A	ENSP00000358338.3
	MAP3K7	ENST00000369325.7	TSL:1	c.121-7277C>G		intron	N/A	ENSP00000358331.3

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7658 AN: 152084 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.00698

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0503 AC: 7661 AN: 152202 Hom.: 303 Cov.: 32 AF XY: 0.0497 AC XY: 3700 AN XY: 74418

African (AFR) AF: 0.103 AC: 4276 AN: 41512

American (AMR) AF: 0.0465 AC: 710 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3468

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5178

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4824

European-Finnish (FIN) AF: 0.00698 AC: 74 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0289 AC: 1963 AN: 68014

Other (OTH) AF: 0.0548 AC: 116 AN: 2116

Alfa AF: 0.00450 Hom.: 0

Bravo AF: 0.0560

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.79
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs16883216; hg19: chr6-91288803;