rs41282607

Positions:

• chr22-21763940-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002745.5(MAPK1):​c.*310G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0206 in 152,694 control chromosomes in the GnomAD database, including 59 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 0.020 (59 hom., cov: 32)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: MAPK1 NM_002745.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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]

MAPK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAdExome4 highest population allele frequency = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.*310G>A		3_prime_UTR_variant	9/9	ENST00000215832.11	NP_002736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832	c.*310G>A		3_prime_UTR_variant	9/9	1	NM_002745.5	ENSP00000215832.7
MAPK1	ENST00000491588.1	n.*44G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3112 AN: 152126 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0600 AC: 27 AN: 450 Hom.: 0 Cov.: 0 AF XY: 0.0662 AC XY: 18 AN XY: 272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.0646

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0204 AC: 3111 AN: 152244 Hom.: 59 Cov.: 32 AF XY: 0.0218 AC XY: 1626 AN XY: 74432

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.00589

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0262 Hom.: 14

Bravo AF: 0.0159

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.93

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: rs41282607; hg19: chr22-22118229;