Variant chr5-56875262-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005921.2(MAP3K1):c.1917G>A(p.Leu639=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,132 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 10 hom. )

Consequence

MAP3K1
NM_005921.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.401

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 5-56875262-G-A is Benign according to our data. Variant chr5-56875262-G-A is described in ClinVar as [Benign]. Clinvar id is 539065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.401 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00733 (1116/152292) while in subpopulation AFR AF= 0.0242 (1005/41548). AF 95% confidence interval is 0.0229. There are 21 homozygotes in gnomad4. There are 525 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1116 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAP3K1	NM_005921.2 linkuse as main transcript	c.1917G>A	p.Leu639=	synonymous_variant	10/20	ENST00000399503.4
MAP3K1	XM_047417218.1 linkuse as main transcript	c.1917G>A	p.Leu639=	synonymous_variant	10/18
MAP3K1	XM_047417219.1 linkuse as main transcript	c.1506G>A	p.Leu502=	synonymous_variant	11/21
MAP3K1	XM_047417220.1 linkuse as main transcript	c.1506G>A	p.Leu502=	synonymous_variant	11/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K1	ENST00000399503.4 linkuse as main transcript	c.1917G>A	p.Leu639=	synonymous_variant	10/20	1	NM_005921.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1114

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00237

AC:

591

AN:

249292

Hom.:

AF XY:

0.00171

AC XY:

231

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00113

AC:

1653

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000991

AC XY:

721

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000382

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00733

AC:

1116

AN:

152292

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00340

Hom.:

Bravo

AF:

0.00841

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

46,XY sex reversal 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.3

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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