rs13058

chr22-21763213-A-C

Variant summary

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

The NM_002745.5(MAPK1):c.*1037T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,740 control chromosomes in the GnomAD database, including 209 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 0.050 (209 hom., cov: 32)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: MAPK1 NM_002745.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

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=-0.54).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK1	NM_002745.5	c.*1037T>G		3_prime_UTR_variant	9/9	ENST00000215832.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK1	ENST00000215832.11	c.*1037T>G		3_prime_UTR_variant	9/9	1	NM_002745.5	P1

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7591 AN: 152186 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0298 AC: 13 AN: 436 Hom.: 0 Cov.: 0 AF XY: 0.0346 AC XY: 9 AN XY: 260

Gnomad4 FIN exome AF: 0.0304

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0499 AC: 7604 AN: 152304 Hom.: 209 Cov.: 32 AF XY: 0.0481 AC XY: 3582 AN XY: 74472

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0552 Hom.: 55

Bravo AF: 0.0523

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	17
Dann	Benign	0.81

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: rs13058; hg19: chr22-22117502;