19-18596238-T-C

Position:

• chr19-18596238-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRLF1	NM_004750.5	c.1024+384A>G		intron_variant		ENST00000392386.8	NP_004741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000392386.8	c.1024+384A>G		intron_variant		1	NM_004750.5	ENSP00000376188.2
CRLF1	ENST00000684169.1	c.1024+384A>G		intron_variant				ENSP00000506849.1
CRLF1	ENST00000597131.1	c.445+426A>G		intron_variant		2		ENSP00000470625.1

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

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.322

Alfa AF: 0.345 Hom.: 12217

Bravo AF: 0.333

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.74
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs8107912; hg19: chr19-18707048;