19-18579020-T-C

Variant summary

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

The ENST00000594325.1(CRLF1):n.232+4550A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,976 control chromosomes in the GnomAD database, including 19,029 homozygotes. 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 0.48 (19029 hom., cov: 31)
• Consequence: CRLF1 ENST00000594325.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRLF1	ENST00000594325.1	n.232+4550A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72182 AN: 151860 Hom.: 19014 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 72220 AN: 151976 Hom.: 19029 Cov.: 31 AF XY: 0.480 AC XY: 35618 AN XY: 74272

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.502

Alfa AF: 0.542 Hom.: 24066

Bravo AF: 0.462

Asia WGS AF: 0.569 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.8
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2057649; hg19: chr19-18689830;