rs34503316

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004750.5(CRLF1):c.75_77delGCT(p.Leu26del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,139,378 control chromosomes in the GnomAD database, including 26,591 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3707 hom., cov: 21)

Exomes 𝑓: 0.21 ( 22884 hom. )

Consequence

CRLF1
NM_004750.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.814

Publications

5 publications found

Variant links:

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

CRLF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 19-18606579-GAGC-G is Benign according to our data. Variant chr19-18606579-GAGC-G is described in ClinVar as [Benign]. Clinvar id is 224611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF1	NM_004750.5 link	c.75_77delGCT	p.Leu26del	disruptive_inframe_deletion	Exon 1 of 9	ENST00000392386.8	NP_004741.1	O75462

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRLF1	ENST00000392386.8 link	c.75_77delGCT	p.Leu26del	disruptive_inframe_deletion	Exon 1 of 9	1	NM_004750.5	ENSP00000376188.2	O75462
CRLF1	ENST00000684169.1 link	c.75_77delGCT	p.Leu26del	disruptive_inframe_deletion	Exon 1 of 9			ENSP00000506849.1	A0A804HI12
CRLF1	ENST00000593286.1 link	n.367+793_367+795delGCT		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

31311

AN:

147948

Hom.:

3692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.151

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.0917

AC:

AN:

120

AF XY:

0.0641

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.208

AC:

206190

AN:

991362

Hom.:

22884

AF XY:

0.207

AC XY:

96502

AN XY:

466382

show subpopulations

African (AFR)

AF:

0.161

AC:

3211

AN:

19958

American (AMR)

AF:

0.316

AC:

1605

AN:

5076

Ashkenazi Jewish (ASJ)

AF:

0.0985

AC:

1085

AN:

11012

East Asian (EAS)

AF:

0.501

AC:

9192

AN:

18344

South Asian (SAS)

AF:

0.214

AC:

3997

AN:

18676

European-Finnish (FIN)

AF:

0.187

AC:

2689

AN:

14398

Middle Eastern (MID)

AF:

0.130

AC:

325

AN:

2496

European-Non Finnish (NFE)

AF:

0.204

AC:

176032

AN:

864086

Other (OTH)

AF:

0.216

AC:

8054

AN:

37316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8156

16312

24469

32625

40781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.212

AC:

31343

AN:

148016

Hom.:

3707

Cov.:

AF XY:

0.215

AC XY:

15489

AN XY:

72188

show subpopulations

African (AFR)

AF:

0.170

AC:

6922

AN:

40794

American (AMR)

AF:

0.309

AC:

4637

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

364

AN:

3450

East Asian (EAS)

AF:

0.489

AC:

2335

AN:

4774

South Asian (SAS)

AF:

0.219

AC:

1048

AN:

4786

European-Finnish (FIN)

AF:

0.214

AC:

2009

AN:

9408

Middle Eastern (MID)

AF:

0.156

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.200

AC:

13287

AN:

66548

Other (OTH)

AF:

0.227

AC:

467

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1164

2329

3493

4658

5822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.119

Hom.:

192

Bravo

AF:

0.223

Asia WGS

AF:

0.353

AC:

1165

AN:

3316

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Sep 26, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: CRLF1 c.75_77delGCT (p.Leu26del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 0.21 in 1139378 control chromosomes, predominantly at a frequency of 0.5 within the Non-Finnish European subpopulation in the gnomAD database, including 2931 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 458.83 fold of the estimated maximal expected allele frequency for a pathogenic variant in CRLF1 causing Cold-Induced Sweating Syndrome phenotype (0.0011). To our knowledge, no occurrence of c.75_77delGCT in individuals affected with Cold-Induced Sweating Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 224611). Based on the evidence outlined above, the variant was classified as benign. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.81

Mutation Taster

=73/27

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs34503316

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over