rs33330

chr5-56850170-G-Achr5-56850170-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005921.2(MAP3K1):c.483-6430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,120 control chromosomes in the GnomAD database, including 5,630 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 0.24 (5630 hom., cov: 32)
• Consequence: MAP3K1 NM_005921.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537

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]

(HGNC:):

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 = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K1	NM_005921.2	c.483-6430G>A		intron_variant		ENST00000399503.4
MAP3K1	XM_047417218.1	c.483-6430G>A		intron_variant
MAP3K1	XM_047417219.1	c.72-6430G>A		intron_variant
MAP3K1	XM_047417220.1	c.72-6430G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K1	ENST00000399503.4	c.483-6430G>A		intron_variant		1	NM_005921.2	P1
	ENST00000415589.1	n.421+1820C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35974 AN: 152002 Hom.: 5632 Cov.: 32

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.00965

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.282

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 35957 AN: 152120 Hom.: 5630 Cov.: 32 AF XY: 0.228 AC XY: 16934 AN XY: 74380

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.00967

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.277

Alfa AF: 0.325 Hom.: 17233

Bravo AF: 0.226

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.3
Dann	Benign	0.28

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

Other links and lift over

dbSNP: rs33330; hg19: chr5-56145997; COSMIC: COSV68122627;