chr12-57100577-T-G

Variant names:

• chr12-57100577-T-G
• rs10783813
• NM_003153.5:c.1513-487A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003153.5(STAT6):​c.1513-487A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 150,998 control chromosomes in the GnomAD database, including 625 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 0.043 (625 hom., cov: 31)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	NM_003153.5	MANE Select	c.1513-487A>C		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1513-487A>C		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.1513-487A>C		intron	N/A	NP_001171550.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	ENST00000300134.8	TSL:1 MANE Select	c.1513-487A>C		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.1513-487A>C		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.1566+269A>C		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6436 AN: 150882 Hom.: 624 Cov.: 31

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.0221

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0560

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0426 AC: 6440 AN: 150998 Hom.: 625 Cov.: 31 AF XY: 0.0475 AC XY: 3498 AN XY: 73688

African (AFR) AF: 0.00628 AC: 258 AN: 41052

American (AMR) AF: 0.109 AC: 1648 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 194 AN: 3466

East Asian (EAS) AF: 0.409 AC: 2085 AN: 5102

South Asian (SAS) AF: 0.0774 AC: 370 AN: 4780

European-Finnish (FIN) AF: 0.0516 AC: 534 AN: 10354

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0179 AC: 1213 AN: 67878

Other (OTH) AF: 0.0552 AC: 115 AN: 2084

Alfa AF: 0.0347 Hom.: 1083

Bravo AF: 0.0484

Asia WGS AF: 0.195 AC: 674 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.60
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10783813; hg19: chr12-57494360; COSMIC: COSV100273207;