chr12-57102172-C-A

Variant names:

• chr12-57102172-C-A
• rs3024967
• NM_003153.5:c.1512+118G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003153.5(STAT6):​c.1512+118G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 994,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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.1512+118G>T		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1512+118G>T		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.1512+118G>T		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.1512+118G>T		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.1512+118G>T		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000553533.2	TSL:3	c.1512+118G>T		intron	N/A	ENSP00000451546.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 994024 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 504274

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

African (AFR) AF: 0.00 AC: 0 AN: 23676

American (AMR) AF: 0.00 AC: 0 AN: 36614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 37170

South Asian (SAS) AF: 0.00 AC: 0 AN: 67054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3094

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 712808

Other (OTH) AF: 0.00 AC: 0 AN: 44222

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.7
DANN	Benign	0.61
PhyloP100		0.20

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: rs3024967; hg19: chr12-57495955;