rs4489951

Positions:

• chr15-66418556-G-A
• chr15-66418556-G-T

Variant summary

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

The NM_002755.4(MAP2K1):​c.81-16471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,174 control chromosomes in the GnomAD database, including 55,776 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 0.85 (55776 hom., cov: 33)
• Consequence: MAP2K1 NM_002755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K1	NM_002755.4	c.81-16471G>A		intron_variant		ENST00000307102.10	NP_002746.1
MAP2K1	NM_001411065.1	c.15-16471G>A		intron_variant			NP_001397994.1
MAP2K1	XM_011521783.4	c.15-16471G>A		intron_variant			XP_011520085.1
MAP2K1	XM_017022411.3	c.81-16471G>A		intron_variant			XP_016877900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K1	ENST00000307102.10	c.81-16471G>A		intron_variant		1	NM_002755.4	ENSP00000302486	P1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128701 AN: 152056 Hom.: 55736 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.846 AC: 128797 AN: 152174 Hom.: 55776 Cov.: 33 AF XY: 0.850 AC XY: 63263 AN XY: 74410

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.902

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.970

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.865

Alfa AF: 0.907 Hom.: 35661

Bravo AF: 0.837

Asia WGS AF: 0.951 AC: 3304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.42

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: rs4489951; hg19: chr15-66710894;