rs6757272

Positions:

• chr2-200863418-A-G
• chr2-200863418-A-T

Variant summary

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

The ENST00000321356.9(CLK1):​c.-1+1146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,828 control chromosomes in the GnomAD database, including 18,190 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 0.48 (18190 hom., cov: 31)
• Consequence: CLK1 ENST00000321356.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

CLK1 (HGNC:2068): (CDC like kinase 1) This gene encodes a member of the CDC2-like (or LAMMER) family of dual specificity protein kinases. In the nucleus, the encoded protein phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing, releasing them into the nucleoplasm. The choice of splice sites during pre-mRNA processing may be regulated by the concentration of transacting factors, including serine/arginine rich proteins. Therefore, the encoded protein may play an indirect role in governing splice site selection. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLK1	NM_004071.4	c.-1+1146T>C		intron_variant		ENST00000321356.9	NP_004062.2
CLK1	NM_001162407.1	c.126+683T>C		intron_variant			NP_001155879.1
CLK1	NR_027855.2	n.95+1146T>C		intron_variant, non_coding_transcript_variant
CLK1	NR_027856.2	n.95+1146T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLK1	ENST00000321356.9	c.-1+1146T>C		intron_variant		1	NM_004071.4	ENSP00000326830	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72058 AN: 151710 Hom.: 18155 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.475 AC: 72136 AN: 151828 Hom.: 18190 Cov.: 31 AF XY: 0.476 AC XY: 35328 AN XY: 74180

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.440

Alfa AF: 0.461 Hom.: 2069

Bravo AF: 0.466

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.38

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: rs6757272; hg19: chr2-201728141;