rs8036023

chr15-66438947-G-C

Variant summary

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

The NM_002755.4(MAP2K1):c.438+2055G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,058 control chromosomes in the GnomAD database, including 7,571 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 0.31 (7571 hom., cov: 31)
• Consequence: MAP2K1 NM_002755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K1	NM_002755.4	c.438+2055G>C		intron_variant		ENST00000307102.10
MAP2K1	NM_001411065.1	c.372+2055G>C		intron_variant
MAP2K1	XM_011521783.4	c.372+2055G>C		intron_variant
MAP2K1	XM_017022411.3	c.438+2055G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K1	ENST00000307102.10	c.438+2055G>C		intron_variant		1	NM_002755.4	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46479 AN: 151940 Hom.: 7560 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.306 AC: 46525 AN: 152058 Hom.: 7571 Cov.: 31 AF XY: 0.309 AC XY: 22948 AN XY: 74298

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.312

Alfa AF: 0.302 Hom.: 933

Bravo AF: 0.307

Asia WGS AF: 0.344 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.041
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8036023; hg19: chr15-66731285;