rs745212

Variant names:

• chr15-67767841-G-A
• rs745212
• NM_145160.3:c.1135-1761G>A

Variant summary

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

The NM_145160.3(MAP2K5):​c.1135-1761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,874 control chromosomes in the GnomAD database, including 9,767 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 0.36 (9767 hom., cov: 31)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 5 publications found

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1135-1761G>A		intron_variant	Intron 19 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1105-1761G>A		intron_variant	Intron 18 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1027-1761G>A		intron_variant	Intron 19 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1135-1761G>A		intron_variant	Intron 19 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54061 AN: 151756 Hom.: 9754 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.356 AC: 54096 AN: 151874 Hom.: 9767 Cov.: 31 AF XY: 0.363 AC XY: 26970 AN XY: 74208

African (AFR) AF: 0.366 AC: 15148 AN: 41416

American (AMR) AF: 0.284 AC: 4326 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3462

East Asian (EAS) AF: 0.396 AC: 2042 AN: 5158

South Asian (SAS) AF: 0.448 AC: 2154 AN: 4812

European-Finnish (FIN) AF: 0.434 AC: 4565 AN: 10522

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23639 AN: 67930

Other (OTH) AF: 0.337 AC: 712 AN: 2114

Alfa AF: 0.339 Hom.: 14176

Bravo AF: 0.340

Asia WGS AF: 0.396 AC: 1374 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.025
DANN	Benign	0.63
PhyloP100		-3.4
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: rs745212; hg19: chr15-68060179;