Genetic Variant MAP3K7:c.1356+5883G>C (chr6-90530454-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145331.3(MAP3K7):c.1356+5883G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,660 control chromosomes in the GnomAD database, including 10,476 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 0.36 ( 10476 hom., cov: 32)

Consequence

MAP3K7
NM_145331.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

2 publications found

Variant links:

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)

MAP3K7 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3 link	c.1356+5883G>C		intron_variant	Intron 13 of 16	ENST00000369329.8	NP_663304.1	O43318-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8 link	c.1356+5883G>C		intron_variant	Intron 13 of 16	1	NM_145331.3	ENSP00000358335.3		O43318-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55207

AN:

151540

Hom.:

10462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.385

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

GnomAD4 genome

AF:

0.365

AC:

55281

AN:

151660

Hom.:

10476

Cov.:

AF XY:

0.360

AC XY:

26657

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.477

AC:

19719

AN:

41298

American (AMR)

AF:

0.346

AC:

5282

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1618

AN:

3460

East Asian (EAS)

AF:

0.315

AC:

1624

AN:

5162

South Asian (SAS)

AF:

0.423

AC:

2039

AN:

4826

European-Finnish (FIN)

AF:

0.238

AC:

2508

AN:

10552

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21250

AN:

67802

Other (OTH)

AF:

0.390

AC:

822

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1748

3495

5243

6990

8738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.325

Hom.:

1000

Bravo

AF:

0.375

Asia WGS

AF:

0.359

AC:

1249

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.75

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over