19-18594033-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004750.5(CRLF1):c.1255+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 27)
  • Exomes 𝑓: 0.012 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRLF1 NM_004750.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-18594033-C-T is Benign according to our data. Variant chr19-18594033-C-T is described in ClinVar as [Benign]. Clinvar id is 1231570.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRLF1	NM_004750.5	c.1255+32G>A		intron_variant		ENST00000392386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRLF1	ENST00000392386.8	c.1255+32G>A		intron_variant		1	NM_004750.5	P1
CRLF1	ENST00000684169.1	c.1260+32G>A		intron_variant
CRLF1	ENST00000594325.1	n.189+214G>A		intron_variant, non_coding_transcript_variant		3
CRLF1	ENST00000596360.1	n.70+32G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 221 AN: 92050 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00243

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00127

Gnomad ASJ AF: 0.00291

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.000405

Gnomad FIN AF: 0.00563

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.00328

GnomAD3 exomes AF: 0.0322 AC: 2838 AN: 88194 Hom.: 0 AF XY: 0.0294 AC XY: 1435 AN XY: 48856

Gnomad AFR exome AF: 0.0417

Gnomad AMR exome AF: 0.0846

Gnomad ASJ exome AF: 0.0387

Gnomad EAS exome AF: 0.0626

Gnomad SAS exome AF: 0.0264

Gnomad FIN exome AF: 0.00581

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0407

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0116 AC: 3642 AN: 314630 Hom.: 7 Cov.: 3 AF XY: 0.0111 AC XY: 1862 AN XY: 168292

Gnomad4 AFR exome AF: 0.0335

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.0190

Gnomad4 EAS exome AF: 0.00831

Gnomad4 SAS exome AF: 0.0107

Gnomad4 FIN exome AF: 0.00583

Gnomad4 NFE exome AF: 0.00837

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00240 AC: 221 AN: 92102 Hom.: 0 Cov.: 27 AF XY: 0.00277 AC XY: 120 AN XY: 43332

Gnomad4 AFR AF: 0.00242

Gnomad4 AMR AF: 0.00127

Gnomad4 ASJ AF: 0.00291

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.000404

Gnomad4 FIN AF: 0.00563

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.00325

Alfa AF: 0.00447 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.1
Dann	Benign	0.95

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;