NM_003153.5:c.1512+118G>A

Variant names:

• chr12-57102172-C-T
• rs3024967
• NM_003153.5:c.1512+118G>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.1512+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,146,190 control chromosomes in the GnomAD database, including 250 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 (156 hom., cov: 30)
  • Exomes 𝑓: 0.0028 (94 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 1 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0832 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.1512+118G>A		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1512+118G>A		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.1512+118G>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.1512+118G>A		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.1512+118G>A		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.1512+118G>A		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3779 AN: 152062 Hom.: 156 Cov.: 30

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.00276 AC: 2743 AN: 994010 Hom.: 94 AF XY: 0.00244 AC XY: 1229 AN XY: 504266

African (AFR) AF: 0.0865 AC: 2046 AN: 23664

American (AMR) AF: 0.00544 AC: 199 AN: 36614

Ashkenazi Jewish (ASJ) AF: 0.000103 AC: 2 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 37170

South Asian (SAS) AF: 0.000254 AC: 17 AN: 67054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50004

Middle Eastern (MID) AF: 0.00711 AC: 22 AN: 3094

European-Non Finnish (NFE) AF: 0.000226 AC: 161 AN: 712808

Other (OTH) AF: 0.00669 AC: 296 AN: 44220

GnomAD4 genome AF: 0.0249 AC: 3793 AN: 152180 Hom.: 156 Cov.: 30 AF XY: 0.0247 AC XY: 1838 AN XY: 74400

African (AFR) AF: 0.0856 AC: 3552 AN: 41508

American (AMR) AF: 0.0114 AC: 175 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67986

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0190 Hom.: 8

Bravo AF: 0.0285

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.7
DANN	Benign	0.53
PhyloP100		0.20
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: rs3024967; hg19: chr12-57495955;