rs1784223

chr11-65612777-T-C

Variant summary

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

The NM_002419.4(MAP3K11):c.739+241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 403,374 control chromosomes in the GnomAD database, including 21,669 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 0.33 (8901 hom., cov: 33)
  • Exomes 𝑓: 0.31 (12768 hom.)
• Consequence: MAP3K11 NM_002419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

MAP3K11 (HGNC:6850): (mitogen-activated protein kinase kinase kinase 11) The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K11	NM_002419.4	c.739+241A>G		intron_variant		ENST00000309100.8
MAP3K11	XM_047426962.1	c.739+241A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K11	ENST00000309100.8	c.739+241A>G		intron_variant		1	NM_002419.4	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50597 AN: 151998 Hom.: 8904 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.308 AC: 77300 AN: 251256 Hom.: 12768 Cov.: 4 AF XY: 0.305 AC XY: 38989 AN XY: 127686

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.333 AC: 50609 AN: 152118 Hom.: 8901 Cov.: 33 AF XY: 0.318 AC XY: 23674 AN XY: 74388

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.350

Alfa AF: 0.343 Hom.: 7556

Bravo AF: 0.343

Asia WGS AF: 0.142 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.7
Dann	Benign	0.83

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: rs1784223; hg19: chr11-65380248;