12-57096045-C-T

Variant names:

• chr12-57096045-C-T
• rs703817
• NM_003153.5:c.*527G>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.*527G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 154,210 control chromosomes in the GnomAD database, including 13,408 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 0.39 (13218 hom., cov: 32)
  • Exomes 𝑓: 0.41 (190 hom.)
• Consequence: STAT6 NM_003153.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 39 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 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.*527G>A		3_prime_UTR	Exon 22 of 22	NP_003144.3
	STAT6	NR_033659.2		n.3187G>A		non_coding_transcript_exon	Exon 21 of 21
	STAT6	NM_001178078.2		c.*527G>A		3_prime_UTR	Exon 22 of 22	NP_001171549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	ENST00000300134.8	TSL:1 MANE Select	c.*527G>A		3_prime_UTR	Exon 22 of 22	ENSP00000300134.3
	STAT6	ENST00000554764.6	TSL:2	n.*2815G>A		non_coding_transcript_exon	Exon 21 of 21	ENSP00000451909.1
	STAT6	ENST00000555222.5	TSL:2	n.2044G>A		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59164 AN: 151930 Hom.: 13216 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.415 AC: 897 AN: 2162 Hom.: 190 Cov.: 0 AF XY: 0.424 AC XY: 486 AN XY: 1146

African (AFR) AF: 0.167 AC: 14 AN: 84

American (AMR) AF: 0.357 AC: 20 AN: 56

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 20 AN: 56

East Asian (EAS) AF: 0.149 AC: 17 AN: 114

South Asian (SAS) AF: 0.389 AC: 14 AN: 36

European-Finnish (FIN) AF: 0.484 AC: 60 AN: 124

Middle Eastern (MID) AF: 0.313 AC: 5 AN: 16

European-Non Finnish (NFE) AF: 0.445 AC: 689 AN: 1548

Other (OTH) AF: 0.453 AC: 58 AN: 128

GnomAD4 genome AF: 0.389 AC: 59165 AN: 152048 Hom.: 13218 Cov.: 32 AF XY: 0.388 AC XY: 28803 AN XY: 74302

African (AFR) AF: 0.166 AC: 6891 AN: 41476

American (AMR) AF: 0.435 AC: 6646 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1548 AN: 3466

East Asian (EAS) AF: 0.253 AC: 1305 AN: 5154

South Asian (SAS) AF: 0.424 AC: 2043 AN: 4820

European-Finnish (FIN) AF: 0.499 AC: 5279 AN: 10580

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.504 AC: 34224 AN: 67960

Other (OTH) AF: 0.399 AC: 841 AN: 2106

Alfa AF: 0.456 Hom.: 30208

Bravo AF: 0.379

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.79
DANN	Benign	0.55
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs703817; hg19: chr12-57489828;