Variant 12-57099758-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0960

Variant links:

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]

STAT6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
STAT6	NM_003153.5 linkuse as main transcript	c.1744+9A>C		intron_variant		ENST00000300134.8	NP_003144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000300134.8 linkuse as main transcript	c.1744+9A>C		intron_variant		1	NM_003153.5	ENSP00000300134	P1	P42226-1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1566

AN:

150964

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0236

AC XY:

16260

AN XY:

688226

show subpopulations

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.:

Cov.:

AF XY:

0.00980

AC XY:

722

AN XY:

73682

show subpopulations

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.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over