rs41274853

Positions:

• chr9-34551898-G-A
• chr9-34551898-G-C

Variant summary

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

The ENST00000378980.8(CNTFR):​c.*173C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 701,960 control chromosomes in the GnomAD database, including 7,464 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 0.14 (1491 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5973 hom.)
• Consequence: CNTFR ENST00000378980.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

Genes affected

CNTFR (HGNC:2170): (ciliary neurotrophic factor receptor) This gene encodes a member of the type 1 cytokine receptor family. The encoded protein is the ligand-specific component of a tripartite receptor for ciliary neurotrophic factor, which plays a critical role in neuronal cell survival, differentiation and gene expression. Binding of ciliary neurotrophic factor to the encoded protein recruits the transmembrane components of the receptor, gp130 and leukemia inhibitory factor receptor, facilitating signal transduction. Single nucleotide polymorphisms in this gene may be associated with variations in muscle strength, as well as early onset of eating disorders. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

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 = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTFR	NM_147164.3	c.*173C>T		3_prime_UTR_variant	10/10	ENST00000378980.8	NP_671693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTFR	ENST00000378980.8	c.*173C>T		3_prime_UTR_variant	10/10	1	NM_147164.3	ENSP00000368265	P1
CNTFR	ENST00000351266.8	c.*173C>T		3_prime_UTR_variant	9/9	1		ENSP00000242338	P1
CNTFR	ENST00000610543.4	c.*173C>T		3_prime_UTR_variant	10/10	5		ENSP00000480451	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20555 AN: 151990 Hom.: 1494 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.136 AC: 75009 AN: 549852 Hom.: 5973 Cov.: 3 AF XY: 0.138 AC XY: 41013 AN XY: 297194

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.0771

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.135 AC: 20547 AN: 152108 Hom.: 1491 Cov.: 32 AF XY: 0.138 AC XY: 10271 AN XY: 74372

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0830 Hom.: 137

Bravo AF: 0.137

Asia WGS AF: 0.238 AC: 824 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	9.0
DANN	Benign	0.65

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: rs41274853; hg19: chr9-34551896; COSMIC: COSV63634023; COSMIC: COSV63634023;