dbSNP rs205342: MAP3K7:c.1463-407G>A (chr6-90519726-C-T) – 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.1463-407G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,708 control chromosomes in the GnomAD database, including 37,681 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 0.70 ( 37681 hom., cov: 31)

Consequence

MAP3K7
NM_145331.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.139

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:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3 link	c.1463-407G>A		intron_variant	Intron 14 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.1463-407G>A		intron_variant	Intron 14 of 16	1	NM_145331.3	ENSP00000358335.3		O43318-1

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106410

AN:

151590

Hom.:

37667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.744

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

GnomAD4 genome

AF:

0.702

AC:

106468

AN:

151708

Hom.:

37681

Cov.:

AF XY:

0.696

AC XY:

51575

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.749

AC:

31020

AN:

41428

American (AMR)

AF:

0.645

AC:

9808

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.814

AC:

2810

AN:

3454

East Asian (EAS)

AF:

0.469

AC:

2409

AN:

5136

South Asian (SAS)

AF:

0.694

AC:

3341

AN:

4814

European-Finnish (FIN)

AF:

0.638

AC:

6724

AN:

10536

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.707

AC:

47961

AN:

67810

Other (OTH)

AF:

0.748

AC:

1581

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1620

3239

4859

6478

8098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.708

Hom.:

4946

Bravo

AF:

0.701

Asia WGS

AF:

0.632

AC:

2199

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

(source)

DANN

Benign

0.70

PhyloP100

-0.14

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