rs7286558

Positions:

• chr22-21825894-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.120-18048G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,242 control chromosomes in the GnomAD database, including 188 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 0.044 (188 hom., cov: 32)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.120-18048G>A		intron_variant		ENST00000215832.11	NP_002736.3
MAPK1	NM_138957.3	c.120-18048G>A		intron_variant			NP_620407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11	c.120-18048G>A		intron_variant		1	NM_002745.5	ENSP00000215832	P1
MAPK1	ENST00000398822.7	c.120-18048G>A		intron_variant		1		ENSP00000381803	P1
MAPK1	ENST00000544786.1	c.120-18048G>A		intron_variant		1		ENSP00000440842
	ENST00000687533.1	n.279+8726C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6729 AN: 152126 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0544

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

GnomAD4 genome AF: 0.0443 AC: 6737 AN: 152242 Hom.: 188 Cov.: 32 AF XY: 0.0428 AC XY: 3185 AN XY: 74434

Gnomad4 AFR AF: 0.0233

Gnomad4 AMR AF: 0.0600

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0299

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0555

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0504 Hom.: 79

Bravo AF: 0.0454

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.74

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: rs7286558; hg19: chr22-22180183;