rs3730158

Variant names:

• chr10-48409974-A-G
• rs3730158
• NM_001323329.2:c.311+37A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-48409974-A-G
• chr10-48409974-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323329.2(MAPK8):​c.311+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 1,607,790 control chromosomes in the GnomAD database, including 5,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (617 hom., cov: 32)
  • Exomes 𝑓: 0.060 (4615 hom.)
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.145
• Publications: 4 publications found

Genes affected

MAPK8 (HGNC:6881): (mitogen-activated protein kinase 8) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-48409974-A-G is Benign according to our data. Variant chr10-48409974-A-G is described in ClinVar as Benign. ClinVar VariationId is 1259128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323329.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	NM_001323329.2	MANE Select	c.311+37A>G		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.311+37A>G		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.311+37A>G		intron	N/A	NP_001310251.1	P45983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.311+37A>G		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.311+37A>G		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.311+37A>G		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8864 AN: 152128 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0618

GnomAD2 exomes AF: 0.0905 AC: 22209 AN: 245450 AF XY: 0.0875

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.0698

Gnomad EAS exome AF: 0.0285

Gnomad FIN exome AF: 0.0420

Gnomad NFE exome AF: 0.0451

Gnomad OTH exome AF: 0.0800

GnomAD4 exome AF: 0.0596 AC: 86735 AN: 1455544 Hom.: 4615 Cov.: 30 AF XY: 0.0616 AC XY: 44552 AN XY: 723742

African (AFR) AF: 0.0125 AC: 414 AN: 33120

American (AMR) AF: 0.269 AC: 11758 AN: 43780

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 1838 AN: 25930

East Asian (EAS) AF: 0.0172 AC: 683 AN: 39610

South Asian (SAS) AF: 0.163 AC: 13769 AN: 84330

European-Finnish (FIN) AF: 0.0463 AC: 2469 AN: 53340

Middle Eastern (MID) AF: 0.0366 AC: 210 AN: 5742

European-Non Finnish (NFE) AF: 0.0467 AC: 51864 AN: 1109550

Other (OTH) AF: 0.0620 AC: 3730 AN: 60142

GnomAD4 genome AF: 0.0583 AC: 8874 AN: 152246 Hom.: 617 Cov.: 32 AF XY: 0.0635 AC XY: 4727 AN XY: 74436

African (AFR) AF: 0.0163 AC: 679 AN: 41552

American (AMR) AF: 0.214 AC: 3269 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.0273 AC: 142 AN: 5192

South Asian (SAS) AF: 0.163 AC: 788 AN: 4822

European-Finnish (FIN) AF: 0.0415 AC: 439 AN: 10590

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0460 AC: 3131 AN: 68008

Other (OTH) AF: 0.0645 AC: 136 AN: 2110

Alfa AF: 0.0537 Hom.: 67

Bravo AF: 0.0653

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.72
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3730158; hg19: chr10-49618017; COSMIC: COSV64408951;