rs1933934

Positions:

• chr1-46569256-T-C

Variant summary

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

The NM_001135553.4(MKNK1):​c.458-758A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,282 control chromosomes in the GnomAD database, including 8,491 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 0.32 (8489 hom., cov: 33)
  • Exomes 𝑓: 0.21 (2 hom.)
• Consequence: MKNK1 NM_001135553.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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]

MKNK1-AS1 (HGNC:44129): (MKNK1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKNK1	NM_001135553.4	c.458-758A>G		intron_variant		ENST00000371945.10
MKNK1-AS1	NR_038403.1	n.1446T>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKNK1	ENST00000371945.10	c.458-758A>G		intron_variant		1	NM_001135553.4	P1
MKNK1-AS1	ENST00000657773.1	n.509-195T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49115 AN: 152060 Hom.: 8481 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.212 AC: 22 AN: 104 Hom.: 2 Cov.: 0 AF XY: 0.178 AC XY: 16 AN XY: 90

Gnomad4 AFR exome AF: 0.125

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.323 AC: 49155 AN: 152178 Hom.: 8489 Cov.: 33 AF XY: 0.324 AC XY: 24085 AN XY: 74398

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.324

Alfa AF: 0.293 Hom.: 1643

Bravo AF: 0.336

Asia WGS AF: 0.251 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.59

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: rs1933934; hg19: chr1-47034928;