19-18596238-T-C

Variant names:

• chr19-18596238-T-C
• rs8107912
• NM_004750.5:c.1024+384A>G

Variant summary

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

The NM_004750.5(CRLF1):​c.1024+384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,932 control chromosomes in the GnomAD database, including 9,593 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 0.35 (9593 hom., cov: 32)
• Consequence: CRLF1 NM_004750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004750.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF1	NM_004750.5	MANE Select	c.1024+384A>G		intron	N/A	NP_004741.1	O75462

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF1	ENST00000392386.8	TSL:1 MANE Select	c.1024+384A>G		intron	N/A	ENSP00000376188.2	O75462
	CRLF1	ENST00000928241.1		c.1105+384A>G		intron	N/A	ENSP00000598300.1
	CRLF1	ENST00000971859.1		c.1090+384A>G		intron	N/A	ENSP00000641918.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52466 AN: 151814 Hom.: 9567 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.346 AC: 52521 AN: 151932 Hom.: 9593 Cov.: 32 AF XY: 0.342 AC XY: 25424 AN XY: 74268

African (AFR) AF: 0.375 AC: 15546 AN: 41432

American (AMR) AF: 0.238 AC: 3628 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3468

East Asian (EAS) AF: 0.113 AC: 586 AN: 5172

South Asian (SAS) AF: 0.203 AC: 976 AN: 4808

European-Finnish (FIN) AF: 0.430 AC: 4528 AN: 10536

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24935 AN: 67954

Other (OTH) AF: 0.322 AC: 677 AN: 2104

Alfa AF: 0.349 Hom.: 35612

Bravo AF: 0.333

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.74
DANN	Benign	0.91
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8107912; hg19: chr19-18707048;