Variant rs1800169 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000614.4(CNTF):c.115-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,610,680 control chromosomes in the GnomAD database, including 17,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1390 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16024 hom. )

Consequence

CNTF
NM_000614.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.9940

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

CNTF (HGNC:2169): (ciliary neurotrophic factor) The protein encoded by this gene is a polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. A read-through transcript variant composed of the upstream ZFP91 gene and CNTF sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. [provided by RefSeq, Oct 2010]

CNTF links:

ZFP91-CNTF (HGNC:):

ZFP91-CNTF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 11-58624028-G-A is Benign according to our data. Variant chr11-58624028-G-A is described in ClinVar as [Benign]. Clinvar id is 17493.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTF	NM_000614.4 linkuse as main transcript	c.115-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361987.6	NP_000605.1
ZFP91-CNTF	NR_024091.1 linkuse as main transcript	n.1845-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTF	ENST00000361987.6 linkuse as main transcript	c.115-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000614.4	ENSP00000355370	P1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18923

AN:

151872

Hom.:

1388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.149

AC:

36652

AN:

245810

Hom.:

2884

AF XY:

0.154

AC XY:

20452

AN XY:

133024

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.146

AC:

213128

AN:

1458690

Hom.:

16024

Cov.:

AF XY:

0.148

AC XY:

107327

AN XY:

725576

show subpopulations

Gnomad4 AFR exome

AF:

0.0462

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.125

AC:

18927

AN:

151990

Hom.:

1390

Cov.:

AF XY:

0.128

AC XY:

9504

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0494

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.141

Hom.:

3741

Bravo

AF:

0.120

Asia WGS

AF:

0.114

AC:

394

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

CILIARY NEUROTROPHIC FACTOR POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.92

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.99

Position offset: 2

DS_AL_spliceai

0.70

Position offset: 6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over