6-90586701-C-G

Variant names:

• chr6-90586701-C-G
• rs282070
• NM_145331.3:c.120+63G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145331.3(MAP3K7):​c.120+63G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,537,468 control chromosomes in the GnomAD database, including 372,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36428 hom., cov: 34)
  • Exomes 𝑓: 0.69 (336569 hom.)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840
• Publications: 6 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)

LOC124901363 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-90586701-C-G is Benign according to our data. Variant chr6-90586701-C-G is described in ClinVar as [Benign]. Clinvar id is 1241619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.120+63G>C		intron_variant	Intron 1 of 16	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.120+63G>C		intron_variant	Intron 1 of 16	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104822 AN: 152040 Hom.: 36403 Cov.: 34

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.695 AC: 962733 AN: 1385310 Hom.: 336569 AF XY: 0.697 AC XY: 476635 AN XY: 683666

African (AFR) AF: 0.717 AC: 22029 AN: 30732

American (AMR) AF: 0.565 AC: 19178 AN: 33960

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 19606 AN: 24278

East Asian (EAS) AF: 0.472 AC: 16594 AN: 35146

South Asian (SAS) AF: 0.712 AC: 55910 AN: 78530

European-Finnish (FIN) AF: 0.644 AC: 29852 AN: 46330

Middle Eastern (MID) AF: 0.784 AC: 3804 AN: 4850

European-Non Finnish (NFE) AF: 0.704 AC: 755647 AN: 1074124

Other (OTH) AF: 0.699 AC: 40113 AN: 57360

GnomAD4 genome AF: 0.689 AC: 104893 AN: 152158 Hom.: 36428 Cov.: 34 AF XY: 0.684 AC XY: 50851 AN XY: 74380

African (AFR) AF: 0.710 AC: 29476 AN: 41528

American (AMR) AF: 0.637 AC: 9748 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2811 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2403 AN: 5136

South Asian (SAS) AF: 0.693 AC: 3346 AN: 4828

European-Finnish (FIN) AF: 0.637 AC: 6754 AN: 10598

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 48011 AN: 67980

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.698 Hom.: 4616

Bravo AF: 0.687

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.51
PhyloP100		-0.084
PromoterAI		0.0054	Neutral
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: rs282070; hg19: chr6-91296420; COSMIC: COSV65235341;