NM_002419.4:c.2207-93C>G

Variant names:

• chr11-65598721-G-C
• rs7946115
• NM_002419.4:c.2207-93C>G

Variant summary

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

The NM_002419.4(MAP3K11):​c.2207-93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 931,276 control chromosomes in the GnomAD database, including 27,833 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 0.20 (3425 hom., cov: 33)
  • Exomes 𝑓: 0.25 (24408 hom.)
• Consequence: MAP3K11 NM_002419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K11	NM_002419.4	c.2207-93C>G		intron_variant	Intron 9 of 9	ENST00000309100.8	NP_002410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K11	ENST00000309100.8	c.2207-93C>G		intron_variant	Intron 9 of 9	1	NM_002419.4	ENSP00000309597.3
MAP3K11	ENST00000530153.5	c.1436-93C>G		intron_variant	Intron 9 of 9	2		ENSP00000433886.1
MAP3K11	ENST00000532507.5	c.455-93C>G		intron_variant	Intron 4 of 4	2		ENSP00000432068.1
MAP3K11	ENST00000524848.5	n.*675-147C>G		intron_variant	Intron 8 of 8	2		ENSP00000431506.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30611 AN: 152014 Hom.: 3426 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.245 AC: 190934 AN: 779142 Hom.: 24408 AF XY: 0.244 AC XY: 94174 AN XY: 386440

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.201 AC: 30602 AN: 152134 Hom.: 3425 Cov.: 33 AF XY: 0.193 AC XY: 14366 AN XY: 74364

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.206

Alfa AF: 0.111 Hom.: 177

Bravo AF: 0.203

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.78

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: rs7946115; hg19: chr11-65366192;