NM_003153.5:c.117-140G>A

Variant names:

• chr12-57107883-C-T
• rs3024951
• NM_003153.5:c.117-140G>A

Variant summary

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

The NM_003153.5(STAT6):​c.117-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,243,416 control chromosomes in the GnomAD database, including 273 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 0.025 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (106 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 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.117-140G>A		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.117-140G>A		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.117-140G>A		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.117-140G>A		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.117-140G>A		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.117-140G>A		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3845 AN: 152194 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00238 AC: 2595 AN: 1091104 Hom.: 106 AF XY: 0.00208 AC XY: 1122 AN XY: 540442

African (AFR) AF: 0.0852 AC: 2098 AN: 24614

American (AMR) AF: 0.00634 AC: 153 AN: 24128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18452

East Asian (EAS) AF: 0.000175 AC: 6 AN: 34260

South Asian (SAS) AF: 0.000258 AC: 16 AN: 61902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31572

Middle Eastern (MID) AF: 0.00219 AC: 8 AN: 3646

European-Non Finnish (NFE) AF: 0.0000710 AC: 60 AN: 845130

Other (OTH) AF: 0.00536 AC: 254 AN: 47400

GnomAD4 genome AF: 0.0252 AC: 3843 AN: 152312 Hom.: 167 Cov.: 32 AF XY: 0.0240 AC XY: 1789 AN XY: 74484

African (AFR) AF: 0.0882 AC: 3665 AN: 41548

American (AMR) AF: 0.00830 AC: 127 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0106 Hom.: 6

Bravo AF: 0.0286

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.55
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs3024951; hg19: chr12-57501666;