rs1063311

Variant names:

• chr22-21762178-C-T
• rs1063311
• NM_002745.5:c.*2072G>A

Variant summary

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

The NM_002745.5(MAPK1):​c.*2072G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,050 control chromosomes in the GnomAD database, including 10,985 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 0.38 (10985 hom., cov: 32)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: MAPK1 NM_002745.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

Genes affected

MAPK1 (HGNC:6871): (mitogen-activated protein kinase 1) This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), 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. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.*2072G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000215832.11	NP_002736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832	c.*2072G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_002745.5	ENSP00000215832.7

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57053 AN: 151916 Hom.: 10987 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.375 AC: 57074 AN: 152034 Hom.: 10985 Cov.: 32 AF XY: 0.368 AC XY: 27355 AN XY: 74310

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.426

Alfa AF: 0.401 Hom.: 5324

Bravo AF: 0.381

Asia WGS AF: 0.258 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.74
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1063311; hg19: chr22-22116467;