NM_002749.4:c.2370C>T

Variant names:

• chr17-19383150-C-T
• rs2233083
• NM_002749.4:c.2370C>T
• MAPK7 p.Ala790Ala

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002749.4(MAPK7):​c.2370C>T​(p.Ala790Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,614,088 control chromosomes in the GnomAD database, including 365 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 0.0065 (54 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (311 hom.)
• Consequence: MAPK7 NM_002749.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-1.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002749.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK7	NM_002749.4	MANE Select	c.2370C>T	p.Ala790Ala	synonymous	Exon 7 of 7	NP_002740.2
	MAPK7	NM_139033.3		c.2370C>T	p.Ala790Ala	synonymous	Exon 7 of 7	NP_620602.2	Q13164-1
	MAPK7	NM_139034.3		c.2370C>T	p.Ala790Ala	synonymous	Exon 7 of 7	NP_620603.2	Q13164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK7	ENST00000395604.8	TSL:1 MANE Select	c.2370C>T	p.Ala790Ala	synonymous	Exon 7 of 7	ENSP00000378968.3	Q13164-1
	MAPK7	ENST00000308406.9	TSL:1	c.2370C>T	p.Ala790Ala	synonymous	Exon 7 of 7	ENSP00000311005.5	Q13164-1
	MAPK7	ENST00000395602.8	TSL:1	c.2370C>T	p.Ala790Ala	synonymous	Exon 7 of 7	ENSP00000378966.4	Q13164-1

Frequencies

GnomAD3 genomes AF: 0.00654 AC: 995 AN: 152122 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.0111 AC: 2785 AN: 251436 AF XY: 0.00974

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.0133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00429 AC: 6277 AN: 1461848 Hom.: 311 Cov.: 32 AF XY: 0.00413 AC XY: 3005 AN XY: 727222

African (AFR) AF: 0.000896 AC: 30 AN: 33478

American (AMR) AF: 0.0128 AC: 573 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.113 AC: 4495 AN: 39698

South Asian (SAS) AF: 0.00436 AC: 376 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000271 AC: 301 AN: 1111998

Other (OTH) AF: 0.00825 AC: 498 AN: 60396

GnomAD4 genome AF: 0.00652 AC: 993 AN: 152240 Hom.: 54 Cov.: 32 AF XY: 0.00736 AC XY: 548 AN XY: 74436

African (AFR) AF: 0.00166 AC: 69 AN: 41528

American (AMR) AF: 0.0159 AC: 243 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.119 AC: 616 AN: 5174

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00152 Hom.: 7

Bravo AF: 0.00737

Asia WGS AF: 0.0440 AC: 154 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.4
DANN	Benign	0.80
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2233083;

hg19: chr17-19286463;

COSMIC: COSV55190576;

COSMIC: COSV55190576;