Variant rs2239751 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000443053.6(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
ENST00000443053.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0450

Variant links:

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]

CISH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	#exon/exons	MANE	Protein
CISH	NM_145071.4 linkuse as main transcript	c.20+1174A>C	intron_variant		ENST00000348721.4	NP_659508.1
CISH	NM_013324.7 linkuse as main transcript	c.-14A>C	5_prime_UTR_variant	2/4		NP_037456.5
CISH	XM_047447398.1 linkuse as main transcript	c.-14A>C	5_prime_UTR_variant	1/3		XP_047303354.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CISH	ENST00000443053.6 linkuse as main transcript	c.-14A>C	5_prime_UTR_variant	2/4	1		ENSP00000409346		Q9NSE2-3
CISH	ENST00000348721.4 linkuse as main transcript	c.20+1174A>C	intron_variant		1	NM_145071.4	ENSP00000294173	P1	Q9NSE2-1
CISH	ENST00000491847.1 linkuse as main transcript	n.1305A>C	non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.0734

AC:

11157

AN:

152060

Hom.:

1089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00967

Gnomad OTH

AF:

0.0627

GnomAD3 exomes

AF:

0.0963

AC:

15050

AN:

156318

Hom.:

2534

AF XY:

0.0803

AC XY:

6650

AN XY:

82806

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.0165

Gnomad FIN exome

AF:

0.00238

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0688

GnomAD4 exome

AF:

0.0311

AC:

43521

AN:

1399196

Hom.:

4811

Cov.:

AF XY:

0.0292

AC XY:

20117

AN XY:

690116

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.0176

Gnomad4 FIN exome

AF:

0.00272

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0735

AC:

11184

AN:

152178

Hom.:

1095

Cov.:

AF XY:

0.0766

AC XY:

5699

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.0292

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00967

Gnomad4 OTH

AF:

0.0616

Alfa

AF:

0.0383

Hom.:

101

Bravo

AF:

0.0946

Asia WGS

AF:

0.141

AC:

489

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.69

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over