17-19378515-T-G

Variant names:

• chr17-19378515-T-G
• rs2233072
• NM_002749.4:c.-121T>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 22 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 -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	c.-121T>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000395604.8	NP_002740.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82972 AN: 152038 Hom.: 28973 Cov.: 32

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.: 44 AF XY: 0.743 AC XY: 329341 AN XY: 443502

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: 40 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

GnomAD4 genome AF: 0.545 AC: 82962 AN: 152156 Hom.: 28969 Cov.: 32 AF XY: 0.534 AC XY: 39738 AN XY: 74394

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: 31 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

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
DANN	Benign	0.60
PhyloP100		0.20
PromoterAI		0.081	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2233072; hg19: chr17-19281828;