chr22-50259207-G-A

Variant names:

• chr22-50259207-G-A
• rs1076650
• NM_002969.6:c.256-906C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002969.6(MAPK12):​c.256-906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,088 control chromosomes in the GnomAD database, including 12,691 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 0.40 (12691 hom., cov: 33)
• Consequence: MAPK12 NM_002969.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 7 publications found

Genes affected

MAPK12 (HGNC:6874): (mitogen-activated protein kinase 12) Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002969.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK12	NM_002969.6	MANE Select	c.256-906C>T		intron	N/A	NP_002960.2
	MAPK12	NM_001303252.3		c.256-906C>T		intron	N/A	NP_001290181.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK12	ENST00000215659.13	TSL:1 MANE Select	c.256-906C>T		intron	N/A	ENSP00000215659.8
	MAPK12	ENST00000622558.4	TSL:1	c.256-906C>T		intron	N/A	ENSP00000479972.1
	MAPK12	ENST00000395780.5	TSL:1	c.16-906C>T		intron	N/A	ENSP00000379126.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61072 AN: 151970 Hom.: 12656 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.402 AC: 61159 AN: 152088 Hom.: 12691 Cov.: 33 AF XY: 0.410 AC XY: 30457 AN XY: 74342

African (AFR) AF: 0.456 AC: 18921 AN: 41478

American (AMR) AF: 0.489 AC: 7475 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1477 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2380 AN: 5168

South Asian (SAS) AF: 0.492 AC: 2365 AN: 4810

European-Finnish (FIN) AF: 0.391 AC: 4147 AN: 10594

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23118 AN: 67954

Other (OTH) AF: 0.417 AC: 881 AN: 2112

Alfa AF: 0.388 Hom.: 3582

Bravo AF: 0.412

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.63
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1076650; hg19: chr22-50697636;