Genetic Variant NM_145160.3:c.-304T>C (chr15-67543032-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145160.3(MAP2K5):c.-304T>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 0.118 in 413,610 control chromosomes in the GnomAD database, including 3,864 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 0.15 ( 2137 hom., cov: 32)

Exomes 𝑓: 0.10 ( 1727 hom. )

Consequence

MAP2K5
NM_145160.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545

Publications

10 publications found

Variant links:

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]

MAP2K5 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3 link	c.-304T>C		5_prime_UTR_variant	Exon 1 of 22	ENST00000178640.10	NP_660143.1	Q13163-1A0A024R5Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10 link	c.-304T>C		5_prime_UTR_variant	Exon 1 of 22	1	NM_145160.3	ENSP00000178640.5		Q13163-1
MAP2K5	ENST00000560591.5 link	n.-231T>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22313

AN:

152010

Hom.:

2133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0877

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.101

AC:

26525

AN:

261482

Hom.:

1727

Cov.:

AF XY:

0.0999

AC XY:

13691

AN XY:

137026

show subpopulations

African (AFR)

AF:

0.252

AC:

2080

AN:

8248

American (AMR)

AF:

0.0912

AC:

1044

AN:

11452

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

529

AN:

8054

East Asian (EAS)

AF:

0.192

AC:

3212

AN:

16734

South Asian (SAS)

AF:

0.0931

AC:

2828

AN:

30386

European-Finnish (FIN)

AF:

0.133

AC:

2049

AN:

15464

Middle Eastern (MID)

AF:

0.0761

AC:

AN:

1196

European-Non Finnish (NFE)

AF:

0.0842

AC:

13025

AN:

154706

Other (OTH)

AF:

0.109

AC:

1667

AN:

15242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1114

2228

3343

4457

5571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22333

AN:

152128

Hom.:

2137

Cov.:

AF XY:

0.150

AC XY:

11148

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.261

AC:

10814

AN:

41496

American (AMR)

AF:

0.122

AC:

1865

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3468

East Asian (EAS)

AF:

0.202

AC:

1039

AN:

5154

South Asian (SAS)

AF:

0.109

AC:

526

AN:

4830

European-Finnish (FIN)

AF:

0.145

AC:

1537

AN:

10588

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0877

AC:

5964

AN:

67978

Other (OTH)

AF:

0.131

AC:

276

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

932

1864

2795

3727

4659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.114

Hom.:

307

Bravo

AF:

0.150

Asia WGS

AF:

0.127

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.55

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over