rs16886448

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005921.2(MAP3K1):c.1687-46C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,599,424 control chromosomes in the GnomAD database, including 4,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 284 hom., cov: 32)

Exomes 𝑓: 0.070 ( 3789 hom. )

Consequence

MAP3K1
NM_005921.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.453

Publications

18 publications found

Variant links:

Genes affected

MAP3K1 (HGNC:6848): (mitogen-activated protein kinase kinase kinase 1) The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]

MAP3K1 Gene-Disease associations (from GenCC):

46,XY sex reversal 6
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
breast cancer
Inheritance: AD Classification: MODERATE Submitted by: G2P
46,XY complete gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MAP3K1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-56874986-C-G is Benign according to our data. Variant chr5-56874986-C-G is described in ClinVar as Benign. ClinVar VariationId is 1231698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MAP3K1	NM_005921.2 link	c.1687-46C>G	intron_variant	Intron 9 of 19	ENST00000399503.4	NP_005912.1	Q13233
MAP3K1	XM_047417218.1 link	c.1687-46C>G	intron_variant	Intron 9 of 17		XP_047273174.1
MAP3K1	XM_047417219.1 link	c.1276-46C>G	intron_variant	Intron 10 of 20		XP_047273175.1
MAP3K1	XM_047417220.1 link	c.1276-46C>G	intron_variant	Intron 10 of 20		XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4 link	c.1687-46C>G		intron_variant	Intron 9 of 19	1	NM_005921.2	ENSP00000382423.3		Q13233

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9017

AN:

152122

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0569

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0570

Gnomad FIN

AF:

0.0740

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0618

GnomAD2 exomes

AF:

0.0664

AC:

16411

AN:

246970

AF XY:

0.0662

show subpopulations

Gnomad AFR exome

AF:

0.0358

Gnomad AMR exome

AF:

0.0722

Gnomad ASJ exome

AF:

0.0627

Gnomad EAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.0725

Gnomad NFE exome

AF:

0.0663

Gnomad OTH exome

AF:

0.0637

GnomAD4 exome

AF:

0.0702

AC:

101636

AN:

1447184

Hom.:

3789

Cov.:

AF XY:

0.0700

AC XY:

50445

AN XY:

720894

show subpopulations

African (AFR)

AF:

0.0371

AC:

1232

AN:

33186

American (AMR)

AF:

0.0723

AC:

3230

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0622

AC:

1620

AN:

26040

East Asian (EAS)

AF:

0.139

AC:

5501

AN:

39632

South Asian (SAS)

AF:

0.0536

AC:

4606

AN:

85894

European-Finnish (FIN)

AF:

0.0740

AC:

3954

AN:

53406

Middle Eastern (MID)

AF:

0.0397

AC:

227

AN:

5722

European-Non Finnish (NFE)

AF:

0.0703

AC:

77276

AN:

1098680

Other (OTH)

AF:

0.0666

AC:

3990

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

5001

10002

15004

20005

25006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2984

5968

8952

11936

14920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0592

AC:

9018

AN:

152240

Hom.:

284

Cov.:

AF XY:

0.0596

AC XY:

4433

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0385

AC:

1600

AN:

41558

American (AMR)

AF:

0.0568

AC:

869

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3468

East Asian (EAS)

AF:

0.118

AC:

610

AN:

5184

South Asian (SAS)

AF:

0.0564

AC:

272

AN:

4822

European-Finnish (FIN)

AF:

0.0740

AC:

783

AN:

10580

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0661

AC:

4493

AN:

68014

Other (OTH)

AF:

0.0612

AC:

129

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

435

870

1306

1741

2176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0590

Hom.:

Bravo

AF:

0.0589

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

46,XY sex reversal 6

Benign:1

Nov 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.84

CADD

Benign

0.86

(source)

DANN

Benign

0.23

PhyloP100

-0.45

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over