rs10518675

Variant names:

• chr15-52026068-A-C
• rs10518675
• NM_002748.4:c.-632+6692A>C

Variant summary

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

The NM_002748.4(MAPK6):​c.-632+6692A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 152,222 control chromosomes in the GnomAD database, including 1,679 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 0.095 (1679 hom., cov: 33)
• Consequence: MAPK6 NM_002748.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK6	NM_002748.4	c.-632+6692A>C		intron_variant	Intron 1 of 5	ENST00000261845.7	NP_002739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK6	ENST00000261845.7	c.-632+6692A>C		intron_variant	Intron 1 of 5	1	NM_002748.4	ENSP00000261845.5

Frequencies

GnomAD3 genomes AF: 0.0952 AC: 14478 AN: 152104 Hom.: 1674 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.0954 AC: 14529 AN: 152222 Hom.: 1679 Cov.: 33 AF XY: 0.0914 AC XY: 6805 AN XY: 74448

African (AFR) AF: 0.270 AC: 11218 AN: 41506

American (AMR) AF: 0.0908 AC: 1388 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.0776 AC: 403 AN: 5192

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4826

European-Finnish (FIN) AF: 0.0176 AC: 187 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0146 AC: 995 AN: 68006

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0416 Hom.: 377

Bravo AF: 0.110

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.46
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518675; hg19: chr15-52318265;