rs9610417

chr22-21845681-C-T

Variant summary

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

The NM_002745.5(MAPK1):c.119+21641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,188 control chromosomes in the GnomAD database, including 2,786 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 0.18 (2786 hom., cov: 32)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK1	NM_002745.5	c.119+21641G>A		intron_variant		ENST00000215832.11
MAPK1	NM_138957.3	c.119+21641G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK1	ENST00000215832.11	c.119+21641G>A		intron_variant		1	NM_002745.5	P1
MAPK1	ENST00000398822.7	c.119+21641G>A		intron_variant		1		P1
MAPK1	ENST00000544786.1	c.119+21641G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27043 AN: 152070 Hom.: 2782 Cov.: 32

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.178 AC: 27048 AN: 152188 Hom.: 2786 Cov.: 32 AF XY: 0.175 AC XY: 13008 AN XY: 74414

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.204

Alfa AF: 0.223 Hom.: 6075

Bravo AF: 0.173

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.1
Dann	Benign	0.65

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: rs9610417; hg19: chr22-22199970;