rs1258012

Positions:

• chr1-46606472-A-G

Variant summary

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

The ENST00000531769.6(MKNK1):​c.-171+10239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,088 control chromosomes in the GnomAD database, including 16,506 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 0.46 (16506 hom., cov: 33)
• Consequence: MKNK1 ENST00000531769.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

MKNK1 (HGNC:7110): (MAPK interacting serine/threonine kinase 1) This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKNK1	ENST00000531769.6	c.-171+10239T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69310 AN: 151970 Hom.: 16491 Cov.: 33

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.456 AC: 69370 AN: 152088 Hom.: 16506 Cov.: 33 AF XY: 0.447 AC XY: 33234 AN XY: 74332

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.449

Alfa AF: 0.485 Hom.: 2672

Bravo AF: 0.457

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1258012; hg19: chr1-47072144;