Variant chr5-56880818-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005921.2(MAP3K1):c.2179+16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,581,146 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 24 hom. )

Consequence

MAP3K1
NM_005921.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.191

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-56880818-T-G is Benign according to our data. Variant chr5-56880818-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 445450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00348 (530/152264) while in subpopulation NFE AF= 0.00575 (391/68012). AF 95% confidence interval is 0.00528. There are 1 homozygotes in gnomad4. There are 229 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 530 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MAP3K1	NM_005921.2 linkuse as main transcript	c.2179+16T>G	intron_variant	ENST00000399503.4
MAP3K1	XM_047417218.1 linkuse as main transcript	c.2179+16T>G	intron_variant
MAP3K1	XM_047417219.1 linkuse as main transcript	c.1768+16T>G	intron_variant
MAP3K1	XM_047417220.1 linkuse as main transcript	c.1768+16T>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K1	ENST00000399503.4 linkuse as main transcript	c.2179+16T>G		intron_variant		1	NM_005921.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

530

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.0429

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00575

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00318

AC:

788

AN:

247550

Hom.:

AF XY:

0.00330

AC XY:

443

AN XY:

134264

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00240

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00276

Gnomad FIN exome

AF:

0.000932

Gnomad NFE exome

AF:

0.00522

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00516

AC:

7367

AN:

1428882

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

3635

AN XY:

712998

show subpopulations

Gnomad4 AFR exome

AF:

0.000883

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.00217

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.000769

Gnomad4 NFE exome

AF:

0.00614

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00348

AC:

530

AN:

152264

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00575

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00367

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

46,XY sex reversal 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.6

DANN

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over