rs841718

Variant names:

• chr12-57099213-G-A
• rs841718
• NM_003153.5:c.1891+81C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57099213-G-A
• chr12-57099213-G-C
• chr12-57099213-G-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.1891+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,598,900 control chromosomes in the GnomAD database, including 265,026 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 0.50 (19920 hom., cov: 30)
  • Exomes 𝑓: 0.58 (245106 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 59 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 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.1891+81C>T		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1891+81C>T		intron	N/A	NP_001171549.1	P42226-1
	STAT6	NM_001178079.2		c.1891+81C>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.1891+81C>T		intron	N/A	ENSP00000300134.3	P42226-1
	STAT6	ENST00000556155.5	TSL:1	c.1891+81C>T		intron	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553533.2	TSL:3	c.1945+81C>T		intron	N/A	ENSP00000451546.2	H0YJH6

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75402 AN: 151744 Hom.: 19919 Cov.: 30

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.577 AC: 834784 AN: 1447038 Hom.: 245106 Cov.: 29 AF XY: 0.576 AC XY: 414343 AN XY: 719898

African (AFR) AF: 0.312 AC: 10332 AN: 33164

American (AMR) AF: 0.537 AC: 23954 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 14119 AN: 25978

East Asian (EAS) AF: 0.271 AC: 10733 AN: 39554

South Asian (SAS) AF: 0.511 AC: 43882 AN: 85822

European-Finnish (FIN) AF: 0.559 AC: 29362 AN: 52538

Middle Eastern (MID) AF: 0.536 AC: 2999 AN: 5594

European-Non Finnish (NFE) AF: 0.605 AC: 665508 AN: 1099856

Other (OTH) AF: 0.566 AC: 33895 AN: 59904

GnomAD4 genome AF: 0.497 AC: 75420 AN: 151862 Hom.: 19920 Cov.: 30 AF XY: 0.494 AC XY: 36696 AN XY: 74224

African (AFR) AF: 0.319 AC: 13211 AN: 41366

American (AMR) AF: 0.530 AC: 8079 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3464

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5162

South Asian (SAS) AF: 0.510 AC: 2457 AN: 4814

European-Finnish (FIN) AF: 0.546 AC: 5763 AN: 10562

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40739 AN: 67942

Other (OTH) AF: 0.528 AC: 1111 AN: 2106

Alfa AF: 0.566 Hom.: 81918

Bravo AF: 0.491

Asia WGS AF: 0.430 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.78
PhyloP100		-0.17
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)		0.010		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: rs841718; hg19: chr12-57492996; COSMIC: COSV55665681; COSMIC: COSV55665681;