rs3024974

chr12-57098962-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003153.5(STAT6):c.1955+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,612,824 control chromosomes in the GnomAD database, including 7,910 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 0.10 (845 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7065 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5	c.1955+53C>T		intron_variant		ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.1955+53C>T		intron_variant		1	NM_003153.5	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15608 AN: 151960 Hom.: 840 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.127

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: 0.0926

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0961 AC: 140444 AN: 1460746 Hom.: 7065 Cov.: 32 AF XY: 0.0963 AC XY: 69972 AN XY: 726780

Gnomad4 AFR exome AF: 0.0967

Gnomad4 AMR exome AF: 0.0960

Gnomad4 ASJ exome AF: 0.0893

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0923

Gnomad4 OTH exome AF: 0.0972

GnomAD4 genome AF: 0.103 AC: 15651 AN: 152078 Hom.: 845 Cov.: 32 AF XY: 0.105 AC XY: 7821 AN XY: 74352

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0941 Hom.: 732

Bravo AF: 0.102

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.80
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024974; hg19: chr12-57492745; COSMIC: COSV55665564; COSMIC: COSV55665564;