rs3024975

chr12-57098080-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.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

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=-0.99).
• 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.2159+425C>T		intron_variant		ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.2159+425C>T		intron_variant		1	NM_003153.5	P1

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0963 Hom.: 145

Bravo AF: 0.106

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.1
Dann	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024975; hg19: chr12-57491863;