rs149517251

Variant names:

• chr20-20039670-A-G
• rs149517251
• NM_001278628.2:c.1484T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-20039670-A-G
• chr20-20039670-A-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP2 BP4_Moderate BS2

The NM_001278628.2(CRNKL1):​c.1484T>C​(p.Ile495Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CRNKL1 NM_001278628.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.87994 (below the threshold of 3.09). Trascript score misZ: 2.5211 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.07014501).
• BS2: High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278628.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRNKL1	NM_001278628.2	MANE Select	c.1484T>C	p.Ile495Thr	missense	Exon 11 of 14	NP_001265557.1	Q9BZJ0-2
	CRNKL1	NM_016652.6		c.1967T>C	p.Ile656Thr	missense	Exon 12 of 15	NP_057736.4
	CRNKL1	NM_001278625.2		c.1931T>C	p.Ile644Thr	missense	Exon 12 of 15	NP_001265554.1	Q5JY65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRNKL1	ENST00000536226.2	TSL:1 MANE Select	c.1484T>C	p.Ile495Thr	missense	Exon 11 of 14	ENSP00000440733.1	Q9BZJ0-2
	CRNKL1	ENST00000377340.6	TSL:1	c.1967T>C	p.Ile656Thr	missense	Exon 12 of 15	ENSP00000366557.2	Q9BZJ0-1
	CRNKL1	ENST00000377327.8	TSL:1	c.1931T>C	p.Ile644Thr	missense	Exon 12 of 15	ENSP00000366544.4	Q5JY65

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000994 AC: 25 AN: 251426 AF XY: 0.000125

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000116 AC: 170 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 89 AN XY: 727238

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000128 AC: 142 AN: 1112006

Other (OTH) AF: 0.000199 AC: 12 AN: 60396

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74344

African (AFR) AF: 0.0000724 AC: 3 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000869

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.59	N
PhyloP100		3.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.076
Sift	Benign	0.71	T
Sift4G	Benign	0.59	T
Polyphen		0.0040	B
Vest4		0.38
MVP		0.20
MPC		0.34
ClinPred		0.052	T
GERP RS		5.8
Varity_R		0.066
gMVP		0.24
Mutation Taster		=76/24	polymorphism

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: rs149517251; hg19: chr20-20020314;