rs9610271

Variant names:

• chr22-21758238-T-C
• rs9610271
• ENST00000962868.1:c.*655A>G

Variant summary

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

The ENST00000962868.1(MAPK1):​c.*655A>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 0.292 in 152,110 control chromosomes in the GnomAD database, including 7,282 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 0.29 (7280 hom., cov: 32)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: MAPK1 ENST00000962868.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 11 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000962868.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK1	ENST00000962868.1		c.*655A>G		3_prime_UTR	Exon 9 of 9	ENSP00000632927.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44388 AN: 151940 Hom.: 7280 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.308 AC: 16 AN: 52 Hom.: 2 Cov.: 0 AF XY: 0.222 AC XY: 8 AN XY: 36

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.326 AC: 15 AN: 46

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.292 AC: 44395 AN: 152058 Hom.: 7280 Cov.: 32 AF XY: 0.284 AC XY: 21141 AN XY: 74322

African (AFR) AF: 0.164 AC: 6811 AN: 41486

American (AMR) AF: 0.302 AC: 4607 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1528 AN: 3468

East Asian (EAS) AF: 0.100 AC: 520 AN: 5182

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2782 AN: 10560

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25945 AN: 67956

Other (OTH) AF: 0.341 AC: 719 AN: 2110

Alfa AF: 0.358 Hom.: 13003

Bravo AF: 0.290

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.74
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: rs9610271; hg19: chr22-22112527;