chr3-50608362-C-G

Variant names:

• chr3-50608362-C-G
• rs622502
• NM_145071.4:c.241+11G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145071.4(CISH):​c.241+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,586,880 control chromosomes in the GnomAD database, including 616,845 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 0.85 (55365 hom., cov: 33)
  • Exomes 𝑓: 0.88 (561480 hom.)
• Consequence: CISH NM_145071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 12 publications found

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]

ACMG classification

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 = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CISH	NM_145071.4	c.241+11G>C		intron_variant	Intron 2 of 2	ENST00000348721.4	NP_659508.1
CISH	NM_013324.7	c.292+11G>C		intron_variant	Intron 3 of 3		NP_037456.5
CISH	XM_047447398.1	c.292+11G>C		intron_variant	Intron 2 of 2		XP_047303354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CISH	ENST00000348721.4	c.241+11G>C		intron_variant	Intron 2 of 2	1	NM_145071.4	ENSP00000294173.3
CISH	ENST00000443053.6	c.292+11G>C		intron_variant	Intron 3 of 3	1		ENSP00000409346.2
CISH	ENST00000491847.1	n.3389+11G>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129339 AN: 152146 Hom.: 55357 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.872

GnomAD2 exomes AF: 0.889 AC: 203568 AN: 229076 AF XY: 0.891

Gnomad AFR exome AF: 0.759

Gnomad AMR exome AF: 0.922

Gnomad ASJ exome AF: 0.945

Gnomad EAS exome AF: 0.933

Gnomad FIN exome AF: 0.876

Gnomad NFE exome AF: 0.880

Gnomad OTH exome AF: 0.893

GnomAD4 exome AF: 0.884 AC: 1268465 AN: 1434616 Hom.: 561480 Cov.: 34 AF XY: 0.886 AC XY: 630109 AN XY: 711484

African (AFR) AF: 0.753 AC: 24563 AN: 32618

American (AMR) AF: 0.914 AC: 37214 AN: 40714

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 22880 AN: 24242

East Asian (EAS) AF: 0.925 AC: 36513 AN: 39482

South Asian (SAS) AF: 0.918 AC: 75280 AN: 81980

European-Finnish (FIN) AF: 0.874 AC: 45900 AN: 52526

Middle Eastern (MID) AF: 0.933 AC: 5255 AN: 5634

European-Non Finnish (NFE) AF: 0.882 AC: 968664 AN: 1098230

Other (OTH) AF: 0.882 AC: 52196 AN: 59190

GnomAD4 genome AF: 0.850 AC: 129391 AN: 152264 Hom.: 55365 Cov.: 33 AF XY: 0.852 AC XY: 63405 AN XY: 74440

African (AFR) AF: 0.757 AC: 31422 AN: 41526

American (AMR) AF: 0.874 AC: 13378 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3275 AN: 3472

East Asian (EAS) AF: 0.935 AC: 4839 AN: 5174

South Asian (SAS) AF: 0.915 AC: 4418 AN: 4830

European-Finnish (FIN) AF: 0.881 AC: 9357 AN: 10618

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59791 AN: 68018

Other (OTH) AF: 0.870 AC: 1840 AN: 2116

Alfa AF: 0.866 Hom.: 6334

Bravo AF: 0.846

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs622502; hg19: chr3-50645793;