chr19-18594087-C-G

Variant names:

• chr19-18594087-C-G
• NM_004750.5:c.1233G>C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004750.5(CRLF1):​c.1233G>C​(p.Ser411Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,520 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 26)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CRLF1 NM_004750.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=2.56 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF1	NM_004750.5	c.1233G>C	p.Ser411Ser	synonymous_variant	Exon 8 of 9	ENST00000392386.8	NP_004741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF1	ENST00000392386.8	c.1233G>C	p.Ser411Ser	synonymous_variant	Exon 8 of 9	1	NM_004750.5	ENSP00000376188.2
CRLF1	ENST00000684169.1	c.1238G>C	p.Arg413Pro	missense_variant	Exon 8 of 9			ENSP00000506849.1
CRLF1	ENST00000596360.1	n.48G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
CRLF1	ENST00000594325.1	n.189+160G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412520 Hom.: 0 Cov.: 41 AF XY: 0.00000143 AC XY: 1 AN XY: 697994

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-18704897;