rs3024971

Variant names:

• chr12-57099944-T-G
• rs3024971
• NM_003153.5:c.1608-41A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003153.5(STAT6):​c.1608-41A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 1,613,844 control chromosomes in the GnomAD database, including 7,802 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 0.079 (565 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7237 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773
• Publications: 41 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 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.1608-41A>C		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1608-41A>C		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.1608-41A>C		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.1608-41A>C		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.1608-41A>C		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.1662-41A>C		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12051 AN: 151906 Hom.: 564 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0775 AC: 19472 AN: 251160 AF XY: 0.0790

Gnomad AFR exome AF: 0.0435

Gnomad AMR exome AF: 0.0583

Gnomad ASJ exome AF: 0.0645

Gnomad EAS exome AF: 0.0757

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0882

GnomAD4 exome AF: 0.0956 AC: 139818 AN: 1461818 Hom.: 7237 Cov.: 33 AF XY: 0.0946 AC XY: 68767 AN XY: 727206

African (AFR) AF: 0.0457 AC: 1530 AN: 33480

American (AMR) AF: 0.0630 AC: 2818 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 1723 AN: 26134

East Asian (EAS) AF: 0.0529 AC: 2102 AN: 39700

South Asian (SAS) AF: 0.0493 AC: 4248 AN: 86252

European-Finnish (FIN) AF: 0.0432 AC: 2309 AN: 53420

Middle Eastern (MID) AF: 0.126 AC: 727 AN: 5768

European-Non Finnish (NFE) AF: 0.107 AC: 118751 AN: 1111966

Other (OTH) AF: 0.0929 AC: 5610 AN: 60394

GnomAD4 genome AF: 0.0793 AC: 12053 AN: 152026 Hom.: 565 Cov.: 32 AF XY: 0.0772 AC XY: 5736 AN XY: 74326

African (AFR) AF: 0.0466 AC: 1932 AN: 41464

American (AMR) AF: 0.0927 AC: 1415 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3468

East Asian (EAS) AF: 0.0778 AC: 400 AN: 5144

South Asian (SAS) AF: 0.0482 AC: 232 AN: 4810

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7100 AN: 67944

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0871 Hom.: 149

Bravo AF: 0.0817

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.77
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3024971; hg19: chr12-57493727; COSMIC: COSV55665333; COSMIC: COSV55665333;