chr12-57105371-G-C

Variant names:

• chr12-57105371-G-C
• rs3024955
• NM_003153.5:c.813-32C>G

Variant summary

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

The NM_003153.5(STAT6):​c.813-32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 1,610,688 control chromosomes in the GnomAD database, including 943 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 0.044 (471 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (472 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 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.813-32C>G		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.813-32C>G		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.813-32C>G		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.813-32C>G		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.813-32C>G		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.813-32C>G		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6597 AN: 152070 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0121 AC: 3022 AN: 249558 AF XY: 0.00909

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.00796

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000682

Gnomad OTH exome AF: 0.00576

GnomAD4 exome AF: 0.00485 AC: 7070 AN: 1458500 Hom.: 472 Cov.: 31 AF XY: 0.00424 AC XY: 3073 AN XY: 724942

African (AFR) AF: 0.157 AC: 5260 AN: 33398

American (AMR) AF: 0.00939 AC: 419 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 344 AN: 25990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00713 AC: 41 AN: 5752

European-Non Finnish (NFE) AF: 0.000280 AC: 311 AN: 1109546

Other (OTH) AF: 0.0110 AC: 662 AN: 60214

GnomAD4 genome AF: 0.0435 AC: 6627 AN: 152188 Hom.: 471 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74408

African (AFR) AF: 0.150 AC: 6223 AN: 41484

American (AMR) AF: 0.0171 AC: 261 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68010

Other (OTH) AF: 0.0298 AC: 63 AN: 2112

Alfa AF: 0.0255 Hom.: 30

Bravo AF: 0.0493

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		0.12
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: rs3024955; hg19: chr12-57499154;