Variant rs2238647 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004750.5(CRLF1):c.237C>T(p.Asn79Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,605,194 control chromosomes in the GnomAD database, including 41,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3475 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37940 hom. )

Consequence

CRLF1
NM_004750.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.500

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 links:

CRLF1 (HGNC:):

CRLF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 19-18599725-G-A is Benign according to our data. Variant chr19-18599725-G-A is described in ClinVar as [Benign]. Clinvar id is 1255324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18599725-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRLF1	NM_004750.5 linkuse as main transcript	c.237C>T	p.Asn79Asn	synonymous_variant	2/9	ENST00000392386.8	NP_004741.1	O75462

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRLF1	ENST00000392386.8 linkuse as main transcript	c.237C>T	p.Asn79Asn	synonymous_variant	2/9	1	NM_004750.5	ENSP00000376188.2	O75462
CRLF1	ENST00000684169.1 linkuse as main transcript	c.237C>T	p.Asn79Asn	synonymous_variant	2/9			ENSP00000506849.1	A0A804HI12
CRLF1	ENST00000593286.1 linkuse as main transcript	n.489C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29588

AN:

152052

Hom.:

3458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.247

AC:

56766

AN:

229994

Hom.:

8400

AF XY:

0.239

AC XY:

29870

AN XY:

124946

show subpopulations

Gnomad AFR exome

AF:

0.0984

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.498

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.218

AC:

316306

AN:

1453024

Hom.:

37940

Cov.:

AF XY:

0.216

AC XY:

156155

AN XY:

722078

show subpopulations

Gnomad4 AFR exome

AF:

0.0943

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.195

AC:

29623

AN:

152170

Hom.:

3475

Cov.:

AF XY:

0.199

AC XY:

14811

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.294

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.196

Hom.:

5120

Bravo

AF:

0.199

Asia WGS

AF:

0.379

AC:

1317

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 06, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.37

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over