chr19-18594033-C-G

Variant names:

• chr19-18594033-C-G
• rs1568439434
• NM_004750.5:c.1255+32G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004750.5(CRLF1):​c.1255+32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000022 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRLF1 NM_004750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF1	NM_004750.5	c.1255+32G>C		intron_variant	Intron 8 of 8	ENST00000392386.8	NP_004741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000392386.8	c.1255+32G>C		intron_variant	Intron 8 of 8	1	NM_004750.5	ENSP00000376188.2
CRLF1	ENST00000684169.1	c.1260+32G>C		intron_variant	Intron 8 of 8			ENSP00000506849.1
CRLF1	ENST00000594325.1	n.189+214G>C		intron_variant	Intron 1 of 2	3
CRLF1	ENST00000596360.1	n.70+32G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 92916 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000432

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000794 AC: 7 AN: 88194 Hom.: 0 AF XY: 0.000102 AC XY: 5 AN XY: 48856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000416

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000665

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00169 AC: 536 AN: 316964 Hom.: 0 Cov.: 3 AF XY: 0.00189 AC XY: 320 AN XY: 169504

Gnomad4 AFR exome AF: 0.000254

Gnomad4 AMR exome AF: 0.000167

Gnomad4 ASJ exome AF: 0.000297

Gnomad4 EAS exome AF: 0.000419

Gnomad4 SAS exome AF: 0.00380

Gnomad4 FIN exome AF: 0.000933

Gnomad4 NFE exome AF: 0.00163

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000215 AC: 2 AN: 92916 Hom.: 0 Cov.: 27 AF XY: 0.0000457 AC XY: 2 AN XY: 43716

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000432

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.8
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1568439434; hg19: chr19-18704843;