Genetic Variant NM_002749.4:c.-121T>G (chr17-19378515-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002749.4(MAPK7):c.-121T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,094,862 control chromosomes in the GnomAD database, including 301,679 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 0.55 ( 28969 hom., cov: 32)

Exomes 𝑓: 0.75 ( 272710 hom. )

Consequence

MAPK7
NM_002749.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.202

Publications

22 publications found

Variant links:

Genes affected

MAPK7 (HGNC:6880): (mitogen-activated protein kinase 7) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MAPK7 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK7	NM_002749.4 link	c.-121T>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000395604.8	NP_002740.2	Q13164-1A0A024QZ20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK7	ENST00000395604.8 link	c.-121T>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_002749.4	ENSP00000378968.3		Q13164-1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82972

AN:

152038

Hom.:

28973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.828

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.604

GnomAD4 exome

AF:

0.746

AC:

703580

AN:

942706

Hom.:

272710

Cov.:

AF XY:

0.743

AC XY:

329341

AN XY:

443502

show subpopulations

African (AFR)

AF:

0.120

AC:

2203

AN:

18306

American (AMR)

AF:

0.487

AC:

2606

AN:

5346

Ashkenazi Jewish (ASJ)

AF:

0.823

AC:

6785

AN:

8240

East Asian (EAS)

AF:

0.00461

AC:

AN:

8682

South Asian (SAS)

AF:

0.381

AC:

12856

AN:

33774

European-Finnish (FIN)

AF:

0.744

AC:

4359

AN:

5858

Middle Eastern (MID)

AF:

0.633

AC:

1328

AN:

2098

European-Non Finnish (NFE)

AF:

0.787

AC:

650963

AN:

826838

Other (OTH)

AF:

0.669

AC:

22440

AN:

33564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

8905

17810

26715

35620

44525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19292

38584

57876

77168

96460

<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:

0.545

AC:

82962

AN:

152156

Hom.:

28969

Cov.:

AF XY:

0.534

AC XY:

39738

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.166

AC:

6913

AN:

41528

American (AMR)

AF:

0.529

AC:

8102

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.828

AC:

2872

AN:

3470

East Asian (EAS)

AF:

0.00599

AC:

AN:

5176

South Asian (SAS)

AF:

0.340

AC:

1636

AN:

4818

European-Finnish (FIN)

AF:

0.743

AC:

7865

AN:

10582

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.783

AC:

53243

AN:

67968

Other (OTH)

AF:

0.596

AC:

1257

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1334

2669

4003

5338

6672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.701

Hom.:

47197

Bravo

AF:

0.516

Asia WGS

AF:

0.166

AC:

580

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.3

(source)

DANN

Benign

0.60

PhyloP100

0.20

PromoterAI

0.081

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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