15-67787223-C-T

Variant names:

• chr15-67787223-C-T
• rs12593698
• NM_145160.3:c.1242+14471C>T

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_145160.3(MAP2K5):​c.1242+14471C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 152,324 control chromosomes in the GnomAD database, including 684 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 0.082 (684 hom., cov: 33)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1242+14471C>T		intron_variant	Intron 21 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1212+14471C>T		intron_variant	Intron 20 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1134+14471C>T		intron_variant	Intron 21 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1242+14471C>T		intron_variant	Intron 21 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12471 AN: 152206 Hom.: 684 Cov.: 33

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0819 AC: 12468 AN: 152324 Hom.: 684 Cov.: 33 AF XY: 0.0862 AC XY: 6418 AN XY: 74484

African (AFR) AF: 0.0229 AC: 951 AN: 41580

American (AMR) AF: 0.102 AC: 1564 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3468

East Asian (EAS) AF: 0.101 AC: 525 AN: 5190

South Asian (SAS) AF: 0.0987 AC: 476 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1627 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6746 AN: 68030

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0596 Hom.: 69

Bravo AF: 0.0750

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.81
PhyloP100		1.0
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: rs12593698; hg19: chr15-68079561;