2-191031319-T-G

Variant names:

• chr2-191031319-T-G
• rs1517351
• NM_003151.4:c.2111+131A>C

Variant summary

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

The NM_003151.4(STAT4):​c.2111+131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,015,626 control chromosomes in the GnomAD database, including 28,400 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 0.27 (6158 hom., cov: 32)
  • Exomes 𝑓: 0.22 (22242 hom.)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 3 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-AS1 (HGNC:55764): (STAT4 antisense RNA 1)

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 (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.2111+131A>C		intron_variant	Intron 22 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.2111+131A>C		intron_variant	Intron 22 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40547 AN: 151942 Hom.: 6152 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.217 AC: 187372 AN: 863564 Hom.: 22242 Cov.: 11 AF XY: 0.215 AC XY: 93676 AN XY: 436462

African (AFR) AF: 0.416 AC: 8294 AN: 19956

American (AMR) AF: 0.173 AC: 3607 AN: 20894

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 3682 AN: 16988

East Asian (EAS) AF: 0.427 AC: 14268 AN: 33428

South Asian (SAS) AF: 0.139 AC: 7630 AN: 54706

European-Finnish (FIN) AF: 0.233 AC: 10068 AN: 43294

Middle Eastern (MID) AF: 0.273 AC: 1021 AN: 3738

European-Non Finnish (NFE) AF: 0.205 AC: 129379 AN: 630932

Other (OTH) AF: 0.238 AC: 9423 AN: 39628

GnomAD4 genome AF: 0.267 AC: 40586 AN: 152062 Hom.: 6158 Cov.: 32 AF XY: 0.268 AC XY: 19895 AN XY: 74362

African (AFR) AF: 0.404 AC: 16762 AN: 41458

American (AMR) AF: 0.223 AC: 3404 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2198 AN: 5168

South Asian (SAS) AF: 0.151 AC: 730 AN: 4822

European-Finnish (FIN) AF: 0.242 AC: 2557 AN: 10580

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13313 AN: 67962

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.260 Hom.: 3825

Bravo AF: 0.275

Asia WGS AF: 0.272 AC: 945 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.15
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: rs1517351; hg19: chr2-191896045;