rs3788332

Variant names:

• chr22-21817278-G-A
• rs3788332
• NM_002745.5:c.120-9432C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002745.5(MAPK1):​c.120-9432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 140,340 control chromosomes in the GnomAD database, including 16,766 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 0.50 (16766 hom., cov: 31)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• Noonan syndrome 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ENSG00000289564 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.120-9432C>T		intron_variant	Intron 1 of 8	ENST00000215832.11	NP_002736.3
MAPK1	NM_138957.3	c.120-9432C>T		intron_variant	Intron 1 of 7		NP_620407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11	c.120-9432C>T		intron_variant	Intron 1 of 8	1	NM_002745.5	ENSP00000215832.7
MAPK1	ENST00000398822.7	c.120-9432C>T		intron_variant	Intron 1 of 7	1		ENSP00000381803.3
MAPK1	ENST00000544786.1	c.120-9432C>T		intron_variant	Intron 1 of 6	1		ENSP00000440842.1
ENSG00000289564	ENST00000687533.2	n.286+110G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 69946 AN: 140210 Hom.: 16761 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.499 AC: 69994 AN: 140340 Hom.: 16766 Cov.: 31 AF XY: 0.499 AC XY: 33956 AN XY: 68076

African (AFR) AF: 0.386 AC: 13823 AN: 35816

American (AMR) AF: 0.609 AC: 8757 AN: 14380

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2112 AN: 3390

East Asian (EAS) AF: 0.483 AC: 2329 AN: 4820

South Asian (SAS) AF: 0.528 AC: 2270 AN: 4302

European-Finnish (FIN) AF: 0.417 AC: 3836 AN: 9210

Middle Eastern (MID) AF: 0.624 AC: 181 AN: 290

European-Non Finnish (NFE) AF: 0.538 AC: 35150 AN: 65284

Other (OTH) AF: 0.561 AC: 1113 AN: 1984

Alfa AF: 0.477 Hom.: 2256

Bravo AF: 0.470

Asia WGS AF: 0.453 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3788332; hg19: chr22-22171567;