19-18594255-G-C

Variant names:

• chr19-18594255-G-C
• NM_004750.5:c.1204C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004750.5(CRLF1):​c.1204C>G​(p.Arg402Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRLF1 NM_004750.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

Genes affected

CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF1	NM_004750.5	c.1204C>G	p.Arg402Gly	missense_variant	Exon 7 of 9	ENST00000392386.8	NP_004741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000392386.8	c.1204C>G	p.Arg402Gly	missense_variant	Exon 7 of 9	1	NM_004750.5	ENSP00000376188.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460704 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 726652

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.96	D
Vest4		0.76
MutPred		0.46		Loss of sheet (P = 0.0104);
MVP		0.88
MPC		1.3
ClinPred		0.96	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-18705065;