rs7249956

Positions:

• chr19-18604393-C-A
• chr19-18604393-C-T

Variant summary

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

The NM_004750.5(CRLF1):​c.115+2149G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,196 control chromosomes in the GnomAD database, including 3,995 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 0.22 (3995 hom., cov: 33)
• Consequence: CRLF1 NM_004750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRLF1	NM_004750.5	c.115+2149G>T		intron_variant		ENST00000392386.8	NP_004741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000392386.8	c.115+2149G>T		intron_variant		1	NM_004750.5	ENSP00000376188	P1
CRLF1	ENST00000684169.1	c.115+2149G>T		intron_variant				ENSP00000506849
CRLF1	ENST00000593286.1	n.367+2982G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33095 AN: 152078 Hom.: 3971 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.218 AC: 33161 AN: 152196 Hom.: 3995 Cov.: 33 AF XY: 0.221 AC XY: 16462 AN XY: 74418

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.233

Alfa AF: 0.202 Hom.: 1086

Bravo AF: 0.226

Asia WGS AF: 0.386 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7249956; hg19: chr19-18715203;