12-57098962-G-A

Variant names:

• chr12-57098962-G-A
• rs3024974
• NM_003153.5:c.1955+53C>T

Variant summary

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

The NM_003153.5(STAT6):​c.1955+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,612,824 control chromosomes in the GnomAD database, including 7,910 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 0.10 (845 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7065 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 38 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 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.1955+53C>T		intron	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.1955+53C>T		intron	N/A	NP_001171549.1
	STAT6	NM_001178079.2		c.1955+53C>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.1955+53C>T		intron	N/A	ENSP00000300134.3
	STAT6	ENST00000556155.5	TSL:1	c.1955+53C>T		intron	N/A	ENSP00000451742.1
	STAT6	ENST00000555222.5	TSL:2	n.869C>T		non_coding_transcript_exon	Exon 4 of 8

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15608 AN: 151960 Hom.: 840 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0961 AC: 140444 AN: 1460746 Hom.: 7065 Cov.: 32 AF XY: 0.0963 AC XY: 69972 AN XY: 726780

African (AFR) AF: 0.0967 AC: 3235 AN: 33464

American (AMR) AF: 0.0960 AC: 4294 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 2333 AN: 26124

East Asian (EAS) AF: 0.160 AC: 6339 AN: 39688

South Asian (SAS) AF: 0.107 AC: 9224 AN: 86232

European-Finnish (FIN) AF: 0.112 AC: 5966 AN: 53420

Middle Eastern (MID) AF: 0.106 AC: 610 AN: 5766

European-Non Finnish (NFE) AF: 0.0923 AC: 102576 AN: 1110972

Other (OTH) AF: 0.0972 AC: 5867 AN: 60360

GnomAD4 genome AF: 0.103 AC: 15651 AN: 152078 Hom.: 845 Cov.: 32 AF XY: 0.105 AC XY: 7821 AN XY: 74352

African (AFR) AF: 0.0972 AC: 4026 AN: 41438

American (AMR) AF: 0.128 AC: 1947 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5174

South Asian (SAS) AF: 0.110 AC: 532 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0926 AC: 6298 AN: 67986

Other (OTH) AF: 0.102 AC: 216 AN: 2112

Alfa AF: 0.0945 Hom.: 960

Bravo AF: 0.102

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.80
DANN	Benign	0.65
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3024974; hg19: chr12-57492745; COSMIC: COSV55665564;