rs252902

Variant names:

• chr5-56820258-A-G
• rs252902
• NM_005921.2:c.482+4203A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-56820258-A-G
• chr5-56820258-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005921.2(MAP3K1):​c.482+4203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 176,670 control chromosomes in the GnomAD database, including 53,408 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 0.77 (45375 hom., cov: 31)
  • Exomes 𝑓: 0.81 (8033 hom.)
• Consequence: MAP3K1 NM_005921.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 15 publications found

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, Labcorp Genetics (formerly Invitae), G2P
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K1	NM_005921.2	MANE Select	c.482+4203A>G		intron	N/A	NP_005912.1	Q13233

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K1	ENST00000399503.4	TSL:1 MANE Select	c.482+4203A>G		intron	N/A	ENSP00000382423.3	Q13233
	MAP3K1	ENST00000872825.1		c.482+4203A>G		intron	N/A	ENSP00000542884.1
	MAP3K1	ENST00000948659.1		c.482+4203A>G		intron	N/A	ENSP00000618718.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116864 AN: 151828 Hom.: 45323 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.767

GnomAD4 exome AF: 0.806 AC: 19922 AN: 24724 Hom.: 8033 AF XY: 0.806 AC XY: 9645 AN XY: 11964

African (AFR) AF: 0.677 AC: 272 AN: 402

American (AMR) AF: 0.700 AC: 21 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 129 AN: 162

East Asian (EAS) AF: 0.670 AC: 71 AN: 106

South Asian (SAS) AF: 0.729 AC: 318 AN: 436

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.778 AC: 28 AN: 36

European-Non Finnish (NFE) AF: 0.812 AC: 18434 AN: 22696

Other (OTH) AF: 0.759 AC: 648 AN: 854

GnomAD4 genome AF: 0.770 AC: 116970 AN: 151946 Hom.: 45375 Cov.: 31 AF XY: 0.765 AC XY: 56828 AN XY: 74264

African (AFR) AF: 0.733 AC: 30366 AN: 41406

American (AMR) AF: 0.675 AC: 10293 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2834 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2998 AN: 5164

South Asian (SAS) AF: 0.771 AC: 3710 AN: 4812

European-Finnish (FIN) AF: 0.808 AC: 8527 AN: 10548

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.820 AC: 55766 AN: 67976

Other (OTH) AF: 0.769 AC: 1620 AN: 2108

Alfa AF: 0.778 Hom.: 22573

Bravo AF: 0.755

Asia WGS AF: 0.698 AC: 2424 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		-0.066
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs252902; hg19: chr5-56116085;