ENST00000556155.5:c.-21-4823G>A

Variant names:

• chr12-57113122-C-T
• rs2598483
• ENST00000556155.5:c.-21-4823G>A

Variant summary

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

The ENST00000556155.5(STAT6):​c.-21-4823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,174 control chromosomes in the GnomAD database, including 584 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 0.075 (584 hom., cov: 32)
• Consequence: STAT6 ENST00000556155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 11 publications found

Genes affected

STAT6 (HGNC:11368): (signal transducer and activator of transcription 6) The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

LOC124902946 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556155.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	ENST00000556155.5	TSL:1	c.-21-4823G>A		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553499.6	TSL:4	c.-21-4823G>A		intron	N/A	ENSP00000451074.2

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11396 AN: 152056 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0748 AC: 11389 AN: 152174 Hom.: 584 Cov.: 32 AF XY: 0.0731 AC XY: 5439 AN XY: 74392

African (AFR) AF: 0.0186 AC: 771 AN: 41508

American (AMR) AF: 0.0754 AC: 1153 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3470

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5174

South Asian (SAS) AF: 0.0928 AC: 448 AN: 4826

European-Finnish (FIN) AF: 0.0820 AC: 870 AN: 10610

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7210 AN: 67988

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.103 Hom.: 1362

Bravo AF: 0.0731

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2598483; hg19: chr12-57506905;