12-57099758-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003153.5(STAT6):c.1744+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,546,726 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (11 hom., cov: 32)
  • Exomes 𝑓: 0.022 (198 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 12-57099758-T-G is Benign according to our data. Variant chr12-57099758-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 778078.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5	c.1744+9A>C		intron_variant		ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.1744+9A>C		intron_variant		1	NM_003153.5	P1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1566 AN: 150964 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.00585

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.00479

Gnomad FIN AF: 0.0100

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.00630

GnomAD4 exome AF: 0.0217 AC: 30237 AN: 1395674 Hom.: 198 Cov.: 32 AF XY: 0.0236 AC XY: 16260 AN XY: 688226

Gnomad4 AFR exome AF: 0.00656

Gnomad4 AMR exome AF: 0.0239

Gnomad4 ASJ exome AF: 0.0353

Gnomad4 EAS exome AF: 0.00501

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0557

Gnomad4 NFE exome AF: 0.0196

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0104 AC: 1570 AN: 151052 Hom.: 11 Cov.: 32 AF XY: 0.00980 AC XY: 722 AN XY: 73682

Gnomad4 AFR AF: 0.00222

Gnomad4 AMR AF: 0.00439

Gnomad4 ASJ AF: 0.00585

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.00500

Gnomad4 FIN AF: 0.0100

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.00577

Alfa AF: 0.0323 Hom.: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	15
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024972; hg19: chr12-57493541; COSMIC: COSV100272465; COSMIC: COSV100272465;