6-90551148-T-C

Variant names:

• chr6-90551148-T-C
• rs157688
• NM_145331.3:c.868-599A>G

Variant summary

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

The ENST00000369329.8(MAP3K7):​c.868-599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,026 control chromosomes in the GnomAD database, including 33,174 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 0.66 (33162 hom., cov: 32)
  • Exomes 𝑓: 0.59 (12 hom.)
• Consequence: MAP3K7 ENST00000369329.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 7 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).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369329.8. 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.868-599A>G		intron	N/A	NP_663304.1
	MAP3K7	NM_003188.4		c.868-599A>G		intron	N/A	NP_003179.1
	MAP3K7	NM_145332.3		c.868-599A>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.868-599A>G		intron	N/A	ENSP00000358335.3
	MAP3K7	ENST00000369332.7	TSL:1	c.868-599A>G		intron	N/A	ENSP00000358338.3
	MAP3K7	ENST00000369325.7	TSL:1	c.868-599A>G		intron	N/A	ENSP00000358331.3

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99896 AN: 151838 Hom.: 33147 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.586 AC: 41 AN: 70 Hom.: 12 Cov.: 0 AF XY: 0.667 AC XY: 28 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.375 AC: 3 AN: 8

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.615 AC: 32 AN: 52

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.658 AC: 99953 AN: 151956 Hom.: 33162 Cov.: 32 AF XY: 0.653 AC XY: 48480 AN XY: 74266

African (AFR) AF: 0.671 AC: 27845 AN: 41470

American (AMR) AF: 0.598 AC: 9122 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2718 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2244 AN: 5178

South Asian (SAS) AF: 0.651 AC: 3142 AN: 4830

European-Finnish (FIN) AF: 0.631 AC: 6664 AN: 10556

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46004 AN: 67876

Other (OTH) AF: 0.694 AC: 1464 AN: 2110

Alfa AF: 0.675 Hom.: 44029

Bravo AF: 0.653

Asia WGS AF: 0.573 AC: 1988 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.032
DANN	Benign	0.53
PhyloP100		-2.7
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: rs157688; hg19: chr6-91260867;