ENST00000526269.2:n.112-556_112-551dupTCTCTC

Variant names:

• chr11-128693941-C-CGAGAGA
• rs57930585
• ENST00000526269.2:n.112-556_112-551dupTCTCTC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000526269.2(SENCR):​n.112-556_112-551dupTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0082 (21 hom., cov: 0)
  • Exomes 𝑓: 0.0060 (0 hom.)
• Consequence: SENCR ENST00000526269.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• Publications: 0 publications found

Genes affected

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

FLI1 (HGNC:3749): (Fli-1 proto-oncogene, ETS transcription factor) This gene encodes a transcription factor containing an ETS DNA-binding domain. The gene can undergo a t(11;22)(q24;q12) translocation with the Ewing sarcoma gene on chromosome 22, which results in a fusion gene that is present in the majority of Ewing sarcoma cases. An acute lymphoblastic leukemia-associated t(4;11)(q21;q23) translocation involving this gene has also been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

FLI1 Gene-Disease associations (from GenCC):

• bleeding disorder, platelet-type, 21

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526269.2. 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
	FLI1	NM_001440369.1		c.-82+845_-82+850dupGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8616_-82+8621dupGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1188_-82+1193dupGAGAGA		intron	N/A	NP_001427300.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENCR	ENST00000526269.2	TSL:1	n.112-556_112-551dupTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-271_-266dupGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-271_-266dupGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.00822 AC: 680 AN: 82770 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.00882

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00282

Gnomad EAS AF: 0.00996

Gnomad SAS AF: 0.00610

Gnomad FIN AF: 0.00409

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00873

Gnomad OTH AF: 0.00604

GnomAD4 exome AF: 0.00596 AC: 555 AN: 93160 Hom.: 0 Cov.: 0 AF XY: 0.00572 AC XY: 253 AN XY: 44236

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

African (AFR) AF: 0.00718 AC: 28 AN: 3900

American (AMR) AF: 0.00366 AC: 10 AN: 2734

Ashkenazi Jewish (ASJ) AF: 0.00187 AC: 10 AN: 5352

East Asian (EAS) AF: 0.0103 AC: 119 AN: 11506

South Asian (SAS) AF: 0.00508 AC: 9 AN: 1772

European-Finnish (FIN) AF: 0.000501 AC: 1 AN: 1996

Middle Eastern (MID) AF: 0.0141 AC: 8 AN: 566

European-Non Finnish (NFE) AF: 0.00562 AC: 326 AN: 57984

Other (OTH) AF: 0.00599 AC: 44 AN: 7350

⚠️ 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 AF: 0.00823 AC: 681 AN: 82792 Hom.: 21 Cov.: 0 AF XY: 0.00794 AC XY: 303 AN XY: 38148

African (AFR) AF: 0.00890 AC: 164 AN: 18418

American (AMR) AF: 0.00818 AC: 64 AN: 7824

Ashkenazi Jewish (ASJ) AF: 0.00282 AC: 7 AN: 2484

East Asian (EAS) AF: 0.0100 AC: 27 AN: 2698

South Asian (SAS) AF: 0.00568 AC: 12 AN: 2114

European-Finnish (FIN) AF: 0.00409 AC: 13 AN: 3180

Middle Eastern (MID) AF: 0.00758 AC: 1 AN: 132

European-Non Finnish (NFE) AF: 0.00873 AC: 386 AN: 44204

Other (OTH) AF: 0.00597 AC: 7 AN: 1172

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71

Splicing

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

Other links and lift over

dbSNP: rs57930585; hg19: chr11-128563836;