rs148059931

Variant names:

• chr9-34552686-C-A
• rs148059931
• NM_147164.3:c.937G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-34552686-C-A
• chr9-34552686-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_147164.3(CNTFR):​c.937G>T​(p.Ala313Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CNTFR NM_147164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0527274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147164.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTFR	NM_147164.3	MANE Select	c.937G>T	p.Ala313Ser	missense	Exon 8 of 10	NP_671693.1	P26992
	CNTFR	NM_001207011.2		c.937G>T	p.Ala313Ser	missense	Exon 8 of 10	NP_001193940.1	P26992
	CNTFR	NM_001842.5		c.937G>T	p.Ala313Ser	missense	Exon 7 of 9	NP_001833.1	P26992

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTFR	ENST00000378980.8	TSL:1 MANE Select	c.937G>T	p.Ala313Ser	missense	Exon 8 of 10	ENSP00000368265.3	P26992
	CNTFR	ENST00000351266.8	TSL:1	c.937G>T	p.Ala313Ser	missense	Exon 7 of 9	ENSP00000242338.4	P26992
	CNTFR	ENST00000868706.1		c.937G>T	p.Ala313Ser	missense	Exon 8 of 10	ENSP00000538765.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000520 AC: 13 AN: 250070 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000678

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1460990 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 726838

African (AFR) AF: 0.000597 AC: 20 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52750

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111900

Other (OTH) AF: 0.0000828 AC: 5 AN: 60368

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74348

African (AFR) AF: 0.000748 AC: 31 AN: 41428

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000234

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.099
Sift	Benign	0.36	T
Sift4G	Benign	0.43	T
Polyphen		0.027	B
Vest4		0.21
MVP		0.33
MPC		0.41
ClinPred		0.026	T
GERP RS		4.6
Varity_R		0.082
gMVP		0.35

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

Other links and lift over

dbSNP: rs148059931; hg19: chr9-34552684;