rs16886403

Positions:

• chr5-56843419-T-C

Variant summary

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

The NM_005921.2(MAP3K1):​c.483-13181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,256 control chromosomes in the GnomAD database, including 1,218 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 0.099 (1218 hom., cov: 32)
• Consequence: MAP3K1 NM_005921.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K1	NM_005921.2	c.483-13181T>C		intron_variant		ENST00000399503.4	NP_005912.1
MAP3K1	XM_047417218.1	c.483-13181T>C		intron_variant			XP_047273174.1
MAP3K1	XM_047417219.1	c.72-13181T>C		intron_variant			XP_047273175.1
MAP3K1	XM_047417220.1	c.72-13181T>C		intron_variant			XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4	c.483-13181T>C		intron_variant		1	NM_005921.2	ENSP00000382423	P1
	ENST00000415589.1	n.422-1206A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15074 AN: 152138 Hom.: 1208 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0992

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

GnomAD4 genome AF: 0.0992 AC: 15102 AN: 152256 Hom.: 1218 Cov.: 32 AF XY: 0.106 AC XY: 7860 AN XY: 74442

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.0879

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.106

Alfa AF: 0.107 Hom.: 288

Bravo AF: 0.0984

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.51

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: rs16886403; hg19: chr5-56139246;