NM_003153.5:c.-21-100G>A

Variant names:

• chr12-57108399-C-T
• rs324011
• NM_003153.5:c.-21-100G>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.-21-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 660,128 control chromosomes in the GnomAD database, including 45,365 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 0.32 (8937 hom., cov: 32)
  • Exomes 𝑓: 0.37 (36428 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 76 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 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.-21-100G>A		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.-21-100G>A		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.-21-100G>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.-21-100G>A		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.-21-100G>A		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.-21-100G>A		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49115 AN: 151978 Hom.: 8928 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.371 AC: 188350 AN: 508032 Hom.: 36428 AF XY: 0.370 AC XY: 100676 AN XY: 271806

African (AFR) AF: 0.159 AC: 2271 AN: 14300

American (AMR) AF: 0.408 AC: 12192 AN: 29850

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 5466 AN: 17014

East Asian (EAS) AF: 0.218 AC: 6705 AN: 30790

South Asian (SAS) AF: 0.363 AC: 20822 AN: 57386

European-Finnish (FIN) AF: 0.441 AC: 13944 AN: 31590

Middle Eastern (MID) AF: 0.198 AC: 520 AN: 2620

European-Non Finnish (NFE) AF: 0.393 AC: 116558 AN: 296504

Other (OTH) AF: 0.353 AC: 9872 AN: 27978

GnomAD4 genome AF: 0.323 AC: 49126 AN: 152096 Hom.: 8937 Cov.: 32 AF XY: 0.323 AC XY: 24047 AN XY: 74358

African (AFR) AF: 0.160 AC: 6631 AN: 41522

American (AMR) AF: 0.373 AC: 5706 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1269 AN: 5158

South Asian (SAS) AF: 0.355 AC: 1714 AN: 4826

European-Finnish (FIN) AF: 0.433 AC: 4570 AN: 10564

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27242 AN: 67954

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.349 Hom.: 19035

Bravo AF: 0.314

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.45
PhyloP100		-0.58
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: rs324011; hg19: chr12-57502182;