rs1076650

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-50259207-G-A
• chr22-50259207-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK12	NM_002969.6	c.256-906C>T		intron_variant	Intron 2 of 11	ENST00000215659.13	NP_002960.2
MAPK12	NM_001303252.3	c.256-906C>T		intron_variant	Intron 2 of 10		NP_001290181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK12	ENST00000215659.13	c.256-906C>T		intron_variant	Intron 2 of 11	1	NM_002969.6	ENSP00000215659.8

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

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.417

Alfa AF: 0.390 Hom.: 1645

Bravo AF: 0.412

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1076650; hg19: chr22-50697636;