rs622502

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-50608362-C-A
• chr3-50608362-C-G
• chr3-50608362-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145071.4(CISH):​c.241+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,587,224 control chromosomes in the GnomAD database, including 9 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 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (9 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).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000468 (671/1434924) while in subpopulation EAS AF = 0.0163 (643/39482). AF 95% confidence interval is 0.0152. There are 9 homozygotes in GnomAdExome4. There are 339 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CISH	NM_145071.4	c.241+11G>T		intron_variant	Intron 2 of 2	ENST00000348721.4	NP_659508.1
CISH	NM_013324.7	c.292+11G>T		intron_variant	Intron 3 of 3		NP_037456.5
CISH	XM_047447398.1	c.292+11G>T		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>T		intron_variant	Intron 2 of 2	1	NM_145071.4	ENSP00000294173.3
CISH	ENST00000443053.6	c.292+11G>T		intron_variant	Intron 3 of 3	1		ENSP00000409346.2
CISH	ENST00000491847.1	n.3389+11G>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00887

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000506 AC: 116 AN: 229076 AF XY: 0.000486

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00617

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000386

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000468 AC: 671 AN: 1434924 Hom.: 9 Cov.: 34 AF XY: 0.000476 AC XY: 339 AN XY: 711638

African (AFR) AF: 0.00 AC: 0 AN: 32640

American (AMR) AF: 0.0000245 AC: 1 AN: 40734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24250

East Asian (EAS) AF: 0.0163 AC: 643 AN: 39482

South Asian (SAS) AF: 0.0000366 AC: 3 AN: 81998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.0000146 AC: 16 AN: 1098452

Other (OTH) AF: 0.000135 AC: 8 AN: 59204

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152300 Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00889 AC: 46 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 6334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.61
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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;