rs2255255

Positions:

• chr20-20052354-T-C

Variant summary

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

The ENST00000377340.6(CRNKL1):​c.472A>G​(p.Thr158Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,646 control chromosomes in the GnomAD database, including 190,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.48 (18129 hom., cov: 33)
  • Exomes 𝑓: 0.48 (172696 hom.)
• Consequence: CRNKL1 ENST00000377340.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8984517E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRNKL1	NM_001278628.2	c.-12A>G		5_prime_UTR_variant	1/14	ENST00000536226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRNKL1	ENST00000536226.2	c.-12A>G		5_prime_UTR_variant	1/14	1	NM_001278628.2	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73616 AN: 151996 Hom.: 18111 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.461

GnomAD3 exomes AF: 0.513 AC: 128806 AN: 250868 Hom.: 33849 AF XY: 0.506 AC XY: 68723 AN XY: 135714

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.463

Gnomad EAS exome AF: 0.731

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.554

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.484 AC: 707382 AN: 1461532 Hom.: 172696 Cov.: 68 AF XY: 0.483 AC XY: 351355 AN XY: 727090

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.484 AC: 73687 AN: 152114 Hom.: 18129 Cov.: 33 AF XY: 0.486 AC XY: 36115 AN XY: 74366

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.461

Alfa AF: 0.480 Hom.: 41628

Bravo AF: 0.485

TwinsUK AF: 0.486 AC: 1801

ALSPAC AF: 0.482 AC: 1856

ESP6500AA AF: 0.441 AC: 1944

ESP6500EA AF: 0.475 AC: 4087

ExAC AF: 0.509 AC: 61772

Asia WGS AF: 0.551 AC: 1918 AN: 3478

EpiCase AF: 0.468

EpiControl AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.75
DEOGEN2	Benign	0.0073	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.13	T;T
MetaRNN	Benign	0.0000019	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.69	.;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.28	N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0	B;B
Vest4		0.035
MPC		0.27
ClinPred		0.00057	T
GERP RS		-0.47
Varity_R		0.031
gMVP		0.097

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: rs2255255; hg19: chr20-20032998; COSMIC: COSV55621375; COSMIC: COSV55621375;