rs3024971

chr12-57099944-T-G

Variant summary

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

The NM_003153.5(STAT6):c.1608-41A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 1,613,844 control chromosomes in the GnomAD database, including 7,802 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 0.079 (565 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7237 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5	c.1608-41A>C		intron_variant		ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.1608-41A>C		intron_variant		1	NM_003153.5	P1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12051 AN: 151906 Hom.: 564 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.0775 AC: 19472 AN: 251160 Hom.: 863 AF XY: 0.0790 AC XY: 10721 AN XY: 135740

Gnomad AFR exome AF: 0.0435

Gnomad AMR exome AF: 0.0583

Gnomad ASJ exome AF: 0.0645

Gnomad EAS exome AF: 0.0757

Gnomad SAS exome AF: 0.0487

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0882

GnomAD4 exome AF: 0.0956 AC: 139818 AN: 1461818 Hom.: 7237 Cov.: 33 AF XY: 0.0946 AC XY: 68767 AN XY: 727206

Gnomad4 AFR exome AF: 0.0457

Gnomad4 AMR exome AF: 0.0630

Gnomad4 ASJ exome AF: 0.0659

Gnomad4 EAS exome AF: 0.0529

Gnomad4 SAS exome AF: 0.0493

Gnomad4 FIN exome AF: 0.0432

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.0929

GnomAD4 genome AF: 0.0793 AC: 12053 AN: 152026 Hom.: 565 Cov.: 32 AF XY: 0.0772 AC XY: 5736 AN XY: 74326

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.0927

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0871 Hom.: 149

Bravo AF: 0.0817

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.5
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024971; hg19: chr12-57493727; COSMIC: COSV55665333; COSMIC: COSV55665333;