chr17-19378515-T-G

Position:

• chr17-19378515-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAPK7	NM_002749.4	c.-121T>G		5_prime_UTR_variant	1/7	ENST00000395604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK7	ENST00000395604.8	c.-121T>G		5_prime_UTR_variant	1/7	1	NM_002749.4	P1

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

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.823

Gnomad4 EAS exome AF: 0.00461

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.669

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.00599

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.596

Alfa AF: 0.728 Hom.: 38289

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

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

LitVar

Other links and lift over

dbSNP: rs2233072; hg19: chr17-19281828;