chr5-56820258-A-G

Position:

• chr5-56820258-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K1	NM_005921.2	c.482+4203A>G		intron_variant		ENST00000399503.4
MAP3K1	XM_047417219.1	c.-488A>G		5_prime_UTR_variant	2/21
MAP3K1	XM_047417218.1	c.482+4203A>G		intron_variant
MAP3K1	XM_047417220.1	c.-20-468A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K1	ENST00000399503.4	c.482+4203A>G		intron_variant		1	NM_005921.2	P1

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

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.796

Gnomad4 EAS exome AF: 0.670

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.759

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

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.769

Alfa AF: 0.762 Hom.: 11354

Bravo AF: 0.755

Asia WGS AF: 0.698 AC: 2424 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs252902; hg19: chr5-56116085;