chr19-18593718-C-T

Position:

• chr19-18593718-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004750.5(CRLF1):​c.1256-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,520,116 control chromosomes in the GnomAD database, including 263,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29927 hom., cov: 33)
  • Exomes 𝑓: 0.58 (233851 hom.)
• Consequence: CRLF1 NM_004750.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0490

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-18593718-C-T is Benign according to our data. Variant chr19-18593718-C-T is described in ClinVar as [Benign]. Clinvar id is 1270588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRLF1	NM_004750.5	c.1256-139G>A		intron_variant		ENST00000392386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRLF1	ENST00000392386.8	c.1256-139G>A		intron_variant		1	NM_004750.5	P1
CRLF1	ENST00000684169.1	c.1261-139G>A		intron_variant
CRLF1	ENST00000594325.1	n.189+529G>A		intron_variant, non_coding_transcript_variant		3
CRLF1	ENST00000596360.1	n.71-139G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94675 AN: 152012 Hom.: 29898 Cov.: 33

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.583 AC: 797161 AN: 1367986 Hom.: 233851 AF XY: 0.579 AC XY: 388757 AN XY: 671720

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.585

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.584

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.623 AC: 94754 AN: 152130 Hom.: 29927 Cov.: 33 AF XY: 0.621 AC XY: 46191 AN XY: 74356

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.588

Alfa AF: 0.609 Hom.: 6146

Bravo AF: 0.620

Asia WGS AF: 0.582 AC: 2021 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7256319; hg19: chr19-18704528;