NM_004750.5:c.698-114A>G

Variant names:

• chr19-18597163-T-C
• rs7250623
• NM_004750.5:c.698-114A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004750.5(CRLF1):​c.698-114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,148,028 control chromosomes in the GnomAD database, including 171,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (21983 hom., cov: 30)
  • Exomes 𝑓: 0.54 (149778 hom.)
• Consequence: CRLF1 NM_004750.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.365
• Publications: 13 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-18597163-T-C is Benign according to our data. Variant chr19-18597163-T-C is described in ClinVar as [Benign]. Clinvar id is 1220821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF1	NM_004750.5	c.698-114A>G		intron_variant	Intron 4 of 8	ENST00000392386.8	NP_004741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000392386.8	c.698-114A>G		intron_variant	Intron 4 of 8	1	NM_004750.5	ENSP00000376188.2
CRLF1	ENST00000684169.1	c.698-114A>G		intron_variant	Intron 4 of 8			ENSP00000506849.1
CRLF1	ENST00000597131.1	c.161-114A>G		intron_variant	Intron 1 of 3	2		ENSP00000470625.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80826 AN: 151676 Hom.: 21944 Cov.: 30

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.544 AC: 542046 AN: 996234 Hom.: 149778 AF XY: 0.540 AC XY: 267211 AN XY: 494838

African (AFR) AF: 0.447 AC: 10163 AN: 22752

American (AMR) AF: 0.550 AC: 14591 AN: 26542

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 8985 AN: 18304

East Asian (EAS) AF: 0.615 AC: 20673 AN: 33610

South Asian (SAS) AF: 0.423 AC: 25800 AN: 60924

European-Finnish (FIN) AF: 0.661 AC: 26592 AN: 40214

Middle Eastern (MID) AF: 0.434 AC: 1483 AN: 3414

European-Non Finnish (NFE) AF: 0.550 AC: 410196 AN: 746372

Other (OTH) AF: 0.534 AC: 23563 AN: 44102

GnomAD4 genome AF: 0.533 AC: 80915 AN: 151794 Hom.: 21983 Cov.: 30 AF XY: 0.534 AC XY: 39581 AN XY: 74184

African (AFR) AF: 0.452 AC: 18705 AN: 41390

American (AMR) AF: 0.530 AC: 8088 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1649 AN: 3464

East Asian (EAS) AF: 0.603 AC: 3105 AN: 5146

South Asian (SAS) AF: 0.423 AC: 2030 AN: 4804

European-Finnish (FIN) AF: 0.659 AC: 6953 AN: 10548

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38621 AN: 67864

Other (OTH) AF: 0.532 AC: 1123 AN: 2110

Alfa AF: 0.554 Hom.: 8839

Bravo AF: 0.523

Asia WGS AF: 0.555 AC: 1926 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 10, 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
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.81
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7250623; hg19: chr19-18707973;