rs2239751
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_013324.7(CISH):c.-14A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,551,374 control chromosomes in the GnomAD database, including 5,906 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 0.073 ( 1095 hom., cov: 33)
Exomes 𝑓: 0.031 ( 4811 hom. )
Consequence
CISH
NM_013324.7 5_prime_UTR
NM_013324.7 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0450
Genes affected
CISH (HGNC:1984): (cytokine inducible SH2 containing protein) The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CISH | NM_145071.4 | c.20+1174A>C | intron_variant | Intron 1 of 2 | ENST00000348721.4 | NP_659508.1 | ||
CISH | NM_013324.7 | c.-14A>C | 5_prime_UTR_variant | Exon 2 of 4 | NP_037456.5 | |||
CISH | XM_047447398.1 | c.-14A>C | 5_prime_UTR_variant | Exon 1 of 3 | XP_047303354.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CISH | ENST00000443053.6 | c.-14A>C | 5_prime_UTR_variant | Exon 2 of 4 | 1 | ENSP00000409346.2 | ||||
CISH | ENST00000348721.4 | c.20+1174A>C | intron_variant | Intron 1 of 2 | 1 | NM_145071.4 | ENSP00000294173.3 | |||
CISH | ENST00000491847.1 | n.1305A>C | non_coding_transcript_exon_variant | Exon 1 of 2 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0734 AC: 11157AN: 152060Hom.: 1089 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
11157
AN:
152060
Hom.:
Cov.:
33
Gnomad AFR
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Gnomad AMI
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GnomAD2 exomes AF: 0.0963 AC: 15050AN: 156318 AF XY: 0.0803 show subpopulations
GnomAD2 exomes
AF:
AC:
15050
AN:
156318
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.0311 AC: 43521AN: 1399196Hom.: 4811 Cov.: 29 AF XY: 0.0292 AC XY: 20117AN XY: 690116 show subpopulations
GnomAD4 exome
AF:
AC:
43521
AN:
1399196
Hom.:
Cov.:
29
AF XY:
AC XY:
20117
AN XY:
690116
Gnomad4 AFR exome
AF:
AC:
4152
AN:
31590
Gnomad4 AMR exome
AF:
AC:
11977
AN:
35702
Gnomad4 ASJ exome
AF:
AC:
477
AN:
25180
Gnomad4 EAS exome
AF:
AC:
11594
AN:
35736
Gnomad4 SAS exome
AF:
AC:
1394
AN:
79228
Gnomad4 FIN exome
AF:
AC:
134
AN:
49272
Gnomad4 NFE exome
AF:
AC:
10834
AN:
1078928
Gnomad4 Remaining exome
AF:
AC:
2768
AN:
57976
Heterozygous variant carriers
0
1940
3880
5819
7759
9699
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
698
1396
2094
2792
3490
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.0735 AC: 11184AN: 152178Hom.: 1095 Cov.: 33 AF XY: 0.0766 AC XY: 5699AN XY: 74416 show subpopulations
GnomAD4 genome
AF:
AC:
11184
AN:
152178
Hom.:
Cov.:
33
AF XY:
AC XY:
5699
AN XY:
74416
Gnomad4 AFR
AF:
AC:
0.123301
AN:
0.123301
Gnomad4 AMR
AF:
AC:
0.219527
AN:
0.219527
Gnomad4 ASJ
AF:
AC:
0.0169931
AN:
0.0169931
Gnomad4 EAS
AF:
AC:
0.329589
AN:
0.329589
Gnomad4 SAS
AF:
AC:
0.0292167
AN:
0.0292167
Gnomad4 FIN
AF:
AC:
0.00150801
AN:
0.00150801
Gnomad4 NFE
AF:
AC:
0.00967476
AN:
0.00967476
Gnomad4 OTH
AF:
AC:
0.061553
AN:
0.061553
Heterozygous variant carriers
0
467
934
1400
1867
2334
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
110
220
330
440
550
<30
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35-40
40-45
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60-65
65-70
70-75
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
489
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=300/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at