19-18581132-A-G

Variant names:

• chr19-18581132-A-G
• rs2314664
• ENST00000594325.1:n.232+2438T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000594325.1(CRLF1):​n.232+2438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,014 control chromosomes in the GnomAD database, including 34,041 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 0.66 (34041 hom., cov: 31)
• Consequence: CRLF1 ENST00000594325.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 27 publications found

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]

CRLF1 Gene-Disease associations (from GenCC):

• Cold-induced sweating syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cold-induced sweating syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• idiopathic achalasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594325.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF1	ENST00000594325.1	TSL:3	n.232+2438T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100470 AN: 151896 Hom.: 33982 Cov.: 31

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.662 AC: 100589 AN: 152014 Hom.: 34041 Cov.: 31 AF XY: 0.658 AC XY: 48918 AN XY: 74296

African (AFR) AF: 0.817 AC: 33897 AN: 41466

American (AMR) AF: 0.629 AC: 9603 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3466

East Asian (EAS) AF: 0.648 AC: 3346 AN: 5164

South Asian (SAS) AF: 0.487 AC: 2347 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6553 AN: 10550

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40999 AN: 67964

Other (OTH) AF: 0.638 AC: 1350 AN: 2116

Alfa AF: 0.607 Hom.: 55828

Bravo AF: 0.672

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2314664; hg19: chr19-18691942;