rs3024975

Variant names:

• chr12-57098080-G-A
• rs3024975
• NM_003153.5:c.2159+425C>T

Variant summary

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

The NM_003153.5(STAT6):​c.2159+425C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,076 control chromosomes in the GnomAD database, including 905 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 0.11 (905 hom., cov: 32)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 9 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]

STAT6 Gene-Disease associations (from GenCC):

• hyper-IgE syndrome 6, autosomal dominant, with recurrent infections

  Inheritance: AD Classification: STRONG Submitted by: ClinGen, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003153.5. 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
	STAT6	NM_003153.5	MANE Select	c.2159+425C>T		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.2159+425C>T		intron	N/A	NP_001171549.1	P42226-1
	STAT6	NM_001178079.2		c.2159+425C>T		intron	N/A	NP_001171550.1	P42226-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	ENST00000300134.8	TSL:1 MANE Select	c.2159+425C>T		intron	N/A	ENSP00000300134.3	P42226-1
	STAT6	ENST00000556155.5	TSL:1	c.2159+425C>T		intron	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553533.2	TSL:3	c.2213+425C>T		intron	N/A	ENSP00000451546.2	H0YJH6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16149 AN: 151958 Hom.: 900 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.106 AC: 16191 AN: 152076 Hom.: 905 Cov.: 32 AF XY: 0.109 AC XY: 8076 AN XY: 74326

African (AFR) AF: 0.109 AC: 4542 AN: 41494

American (AMR) AF: 0.129 AC: 1969 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5170

South Asian (SAS) AF: 0.110 AC: 530 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1195 AN: 10552

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6302 AN: 67996

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.101 Hom.: 299

Bravo AF: 0.106

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.82
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: rs3024975; hg19: chr12-57491863;