Genetic Variant STAT6:c.*707G>A (chr12-57095865-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003153.5(STAT6):c.*707G>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 0.589 in 152,178 control chromosomes in the GnomAD database, including 26,921 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 0.59 ( 26915 hom., cov: 33)

Exomes 𝑓: 0.63 ( 6 hom. )

Consequence

STAT6
NM_003153.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.622

Publications

42 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STAT6	NM_003153.5	MANE Select	c.*707G>A	3_prime_UTR	Exon 22 of 22	NP_003144.3
STAT6	NR_033659.2		n.3367G>A	non_coding_transcript_exon	Exon 21 of 21
STAT6	NM_001178078.2		c.*707G>A	3_prime_UTR	Exon 22 of 22	NP_001171549.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STAT6	ENST00000300134.8	TSL:1 MANE Select	c.*707G>A	3_prime_UTR	Exon 22 of 22	ENSP00000300134.3
STAT6	ENST00000554764.6	TSL:2	n.*2995G>A	non_coding_transcript_exon	Exon 21 of 21	ENSP00000451909.1
STAT6	ENST00000555318.2	TSL:3	n.*1054G>A	non_coding_transcript_exon	Exon 22 of 22	ENSP00000450428.2

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89644

AN:

152036

Hom.:

26906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.532

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.602

GnomAD4 exome

AF:

0.625

AC:

AN:

Hom.:

Cov.:

AF XY:

0.563

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.589

AC:

89684

AN:

152154

Hom.:

26915

Cov.:

AF XY:

0.582

AC XY:

43269

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.531

AC:

22036

AN:

41490

American (AMR)

AF:

0.600

AC:

9177

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

2200

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1743

AN:

5178

South Asian (SAS)

AF:

0.498

AC:

2403

AN:

4826

European-Finnish (FIN)

AF:

0.582

AC:

6156

AN:

10580

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.650

AC:

44185

AN:

67994

Other (OTH)

AF:

0.597

AC:

1261

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1877

3754

5632

7509

9386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.629

Hom.:

49289

Bravo

AF:

0.592

Asia WGS

AF:

0.426

AC:

1483

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.35

(source)

DANN

Benign

0.72

PhyloP100

-0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over