chr15-66387263-G-C

Position:

• chr15-66387263-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002755.4(MAP2K1):​c.-85G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,243,106 control chromosomes in the GnomAD database, including 35,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3356 hom., cov: 33)
  • Exomes 𝑓: 0.24 (32150 hom.)
• Consequence: MAP2K1 NM_002755.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-66387263-G-C is Benign according to our data. Variant chr15-66387263-G-C is described in ClinVar as [Benign]. Clinvar id is 1286889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K1	NM_002755.4	c.-85G>C		5_prime_UTR_variant	1/11	ENST00000307102.10	NP_002746.1
MAP2K1	XM_017022411.3	c.-85G>C		5_prime_UTR_variant	1/10		XP_016877900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K1	ENST00000307102.10	c.-85G>C		5_prime_UTR_variant	1/11	1	NM_002755.4	ENSP00000302486	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28371 AN: 151944 Hom.: 3364 Cov.: 33

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.236 AC: 257139 AN: 1091046 Hom.: 32150 Cov.: 14 AF XY: 0.239 AC XY: 131570 AN XY: 549408

Gnomad4 AFR exome AF: 0.0471

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.186 AC: 28352 AN: 152060 Hom.: 3356 Cov.: 33 AF XY: 0.187 AC XY: 13922 AN XY: 74314

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.198

Alfa AF: 0.225 Hom.: 543

Bravo AF: 0.170

Asia WGS AF: 0.219 AC: 760 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
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: rs112542693; hg19: chr15-66679601;