chr12-57104697-C-T

Variant names:

• chr12-57104697-C-T
• rs3024980
• NM_003153.5:c.1089+29G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003153.5(STAT6):​c.1089+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,613,920 control chromosomes in the GnomAD database, including 149 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 0.0082 (9 hom., cov: 32)
  • Exomes 𝑓: 0.012 (140 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 1247 AD gene.

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.1089+29G>A		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1089+29G>A		intron	N/A	NP_001171549.1	P42226-1
	STAT6	NM_001178079.2		c.1089+29G>A		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.1089+29G>A		intron	N/A	ENSP00000300134.3	P42226-1
	STAT6	ENST00000556155.5	TSL:1	c.1089+29G>A		intron	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553533.2	TSL:3	c.1089+29G>A		intron	N/A	ENSP00000451546.2	H0YJH6

Frequencies

GnomAD3 genomes AF: 0.00820 AC: 1247 AN: 152130 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00890 AC: 2235 AN: 251044 AF XY: 0.00899

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0123

GnomAD4 exome AF: 0.0119 AC: 17420 AN: 1461672 Hom.: 140 Cov.: 31 AF XY: 0.0115 AC XY: 8368 AN XY: 727126

African (AFR) AF: 0.00212 AC: 71 AN: 33478

American (AMR) AF: 0.00255 AC: 114 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00104 AC: 90 AN: 86242

European-Finnish (FIN) AF: 0.0189 AC: 1007 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0141 AC: 15660 AN: 1111870

Other (OTH) AF: 0.00782 AC: 472 AN: 60386

GnomAD4 genome AF: 0.00819 AC: 1247 AN: 152248 Hom.: 9 Cov.: 32 AF XY: 0.00854 AC XY: 636 AN XY: 74442

African (AFR) AF: 0.00234 AC: 97 AN: 41540

American (AMR) AF: 0.00222 AC: 34 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0130 AC: 886 AN: 68006

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00775 Hom.: 2

Bravo AF: 0.00679

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.29
DANN	Benign	0.42
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3024980; hg19: chr12-57498480;