chr1-46606472-A-G

Variant names:

• chr1-46606472-A-G
• rs1258012
• ENST00000531769.6:c.-171+10239T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKNK1	ENST00000531769.6	c.-171+10239T>C		intron_variant	Intron 1 of 4	4		ENSP00000434021.2

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

African (AFR) AF: 0.441 AC: 18290 AN: 41492

American (AMR) AF: 0.437 AC: 6677 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3470

East Asian (EAS) AF: 0.0587 AC: 304 AN: 5180

South Asian (SAS) AF: 0.251 AC: 1212 AN: 4826

European-Finnish (FIN) AF: 0.427 AC: 4512 AN: 10556

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35125 AN: 67960

Other (OTH) AF: 0.449 AC: 950 AN: 2114

Alfa AF: 0.484 Hom.: 2739

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
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1258012; hg19: chr1-47072144;