15-52025949-T-G

Position:

• chr15-52025949-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002748.4(MAPK6):​c.-632+6573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,078 control chromosomes in the GnomAD database, including 44,468 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 0.74 (44468 hom., cov: 32)
• Consequence: MAPK6 NM_002748.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

MAPK6 (HGNC:6879): (mitogen-activated protein kinase 6) The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK6	NM_002748.4	c.-632+6573T>G		intron_variant		ENST00000261845.7	NP_002739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK6	ENST00000261845.7	c.-632+6573T>G		intron_variant		1	NM_002748.4	ENSP00000261845	P1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112638 AN: 151960 Hom.: 44464 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.768

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.741 AC: 112665 AN: 152078 Hom.: 44468 Cov.: 32 AF XY: 0.738 AC XY: 54832 AN XY: 74344

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.765

Alfa AF: 0.856 Hom.: 61429

Bravo AF: 0.723

Asia WGS AF: 0.482 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs10518674; hg19: chr15-52318146;