rs16981483

Variant names:

• chr20-20051023-C-T
• rs16981483
• NM_001278628.2:c.52-401G>A

Variant summary

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

The NM_001278628.2(CRNKL1):​c.52-401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,212 control chromosomes in the GnomAD database, including 758 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 0.092 (758 hom., cov: 33)
• Consequence: CRNKL1 NM_001278628.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758
• Publications: 4 publications found

Genes affected

CRNKL1 (HGNC:15762): (crooked neck pre-mRNA splicing factor 1) The crooked neck (crn) gene of Drosophila is essential for embryogenesis and is thought to be involved in cell cycle progression and pre-mRNA splicing. A protein encoded by this human locus has been found to localize to pre-mRNA splicing complexes in the nucleus and is necessary for pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRNKL1	NM_001278628.2	c.52-401G>A		intron_variant	Intron 1 of 13	ENST00000536226.2	NP_001265557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRNKL1	ENST00000536226.2	c.52-401G>A		intron_variant	Intron 1 of 13	1	NM_001278628.2	ENSP00000440733.1

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13999 AN: 152092 Hom.: 754 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.0921 AC: 14026 AN: 152212 Hom.: 758 Cov.: 33 AF XY: 0.0908 AC XY: 6760 AN XY: 74422

African (AFR) AF: 0.138 AC: 5748 AN: 41520

American (AMR) AF: 0.108 AC: 1644 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3472

East Asian (EAS) AF: 0.118 AC: 614 AN: 5182

South Asian (SAS) AF: 0.0879 AC: 424 AN: 4824

European-Finnish (FIN) AF: 0.0234 AC: 248 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4790 AN: 68006

Other (OTH) AF: 0.0932 AC: 197 AN: 2114

Alfa AF: 0.0805 Hom.: 869

Bravo AF: 0.100

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.73
PhyloP100		0.76
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: rs16981483; hg19: chr20-20031667;