rs11575221

Variant names:

• chr12-56360353-T-G
• rs11575221
• ENST00000826586.1:n.114T>G

Variant summary

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

The ENST00000826586.1(ENSG00000307495):​n.114T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 683,694 control chromosomes in the GnomAD database, including 7,268 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 0.15 (5663 hom., cov: 32)
  • Exomes 𝑓: 0.012 (1605 hom.)
• Consequence: ENSG00000307495 ENST00000826586.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817
• Publications: 8 publications found

Genes affected

ENSG00000307495 (HGNC:):

STAT2 (HGNC:11363): (signal transducer and activator of transcription 2) The protein encoded by this gene is a member of the STAT protein family. 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. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. The protein mediates innate antiviral activity. Mutations in this gene result in Immunodeficiency 44. [provided by RefSeq, Aug 2020]

APOF (HGNC:615): (apolipoprotein F) The product of this gene is one of the minor apolipoproteins found in plasma. This protein forms complexes with lipoproteins and may be involved in transport and/or esterification of cholesterol. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000826586.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT2	NM_005419.4	MANE Select	c.-303A>C		upstream_gene	N/A	NP_005410.1	P52630-3
	APOF	NM_001638.4	MANE Select	c.*872A>C		downstream_gene	N/A	NP_001629.1	Q13790
	STAT2	NM_198332.2		c.-303A>C		upstream_gene	N/A	NP_938146.1	P52630-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000307495	ENST00000826586.1		n.114T>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000307495	ENST00000826587.1		n.343T>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000307495	ENST00000826588.1		n.129T>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22767 AN: 152010 Hom.: 5646 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.0956

GnomAD4 exome AF: 0.0123 AC: 6515 AN: 531566 Hom.: 1605 AF XY: 0.0114 AC XY: 2829 AN XY: 248308

African (AFR) AF: 0.545 AC: 5466 AN: 10026

American (AMR) AF: 0.0433 AC: 27 AN: 624

Ashkenazi Jewish (ASJ) AF: 0.0209 AC: 69 AN: 3296

East Asian (EAS) AF: 0.00 AC: 0 AN: 2210

South Asian (SAS) AF: 0.000190 AC: 2 AN: 10512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 172

Middle Eastern (MID) AF: 0.0263 AC: 26 AN: 988

European-Non Finnish (NFE) AF: 0.000938 AC: 456 AN: 486374

Other (OTH) AF: 0.0270 AC: 469 AN: 17364

GnomAD4 genome AF: 0.150 AC: 22830 AN: 152128 Hom.: 5663 Cov.: 32 AF XY: 0.145 AC XY: 10755 AN XY: 74402

African (AFR) AF: 0.517 AC: 21409 AN: 41436

American (AMR) AF: 0.0630 AC: 963 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

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

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00241 AC: 164 AN: 68014

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.0365 Hom.: 1157

Bravo AF: 0.171

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.57
PhyloP100		-0.82
PromoterAI		-0.052	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11575221;

hg19: chr12-56754137;