19-18581132-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000594325.1(CRLF1):n.232+2438T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,014 control chromosomes in the GnomAD database, including 34,041 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 0.66 (34041 hom., cov: 31)
• Consequence: CRLF1 ENST00000594325.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRLF1	ENST00000594325.1	n.232+2438T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100470 AN: 151896 Hom.: 33982 Cov.: 31

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.662 AC: 100589 AN: 152014 Hom.: 34041 Cov.: 31 AF XY: 0.658 AC XY: 48918 AN XY: 74296

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.638

Alfa AF: 0.600 Hom.: 39223

Bravo AF: 0.672

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2314664; hg19: chr19-18691942;