rs6738544

Variant names:

• chr2-191124630-A-C
• rs6738544
• NM_003151.4:c.273+21983T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-191124630-A-C
• chr2-191124630-A-T

Variant summary

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

The NM_003151.4(STAT4):​c.273+21983T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,804 control chromosomes in the GnomAD database, including 28,927 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 0.61 (28927 hom., cov: 29)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 29 publications found

Genes affected

STAT4 (HGNC:11365): (signal transducer and activator of transcription 4) 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 is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

STAT4 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• disabling pansclerotic morphea of childhood

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300654 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.273+21983T>G		intron_variant	Intron 3 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.273+21983T>G		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92387 AN: 151688 Hom.: 28893 Cov.: 29

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.604

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92463 AN: 151804 Hom.: 28927 Cov.: 29 AF XY: 0.618 AC XY: 45863 AN XY: 74196

African (AFR) AF: 0.476 AC: 19720 AN: 41390

American (AMR) AF: 0.696 AC: 10616 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3464

East Asian (EAS) AF: 0.741 AC: 3820 AN: 5154

South Asian (SAS) AF: 0.780 AC: 3747 AN: 4804

European-Finnish (FIN) AF: 0.720 AC: 7578 AN: 10526

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42770 AN: 67920

Other (OTH) AF: 0.607 AC: 1276 AN: 2102

Alfa AF: 0.616 Hom.: 95305

Bravo AF: 0.600

Asia WGS AF: 0.778 AC: 2705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.95
DANN	Benign	0.54
PhyloP100		-0.85
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: rs6738544; hg19: chr2-191989356;