NM_002017.5:c.30G>A

Variant names:

• chr11-128758126-G-A
• rs756528214
• NM_002017.5:c.30G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_002017.5(FLI1):​c.30G>A​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: FLI1 NM_002017.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.976
• Publications: 0 publications found

Genes affected

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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 11-128758126-G-A is Benign according to our data. Variant chr11-128758126-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2889011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.976 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000092 (14/152136) while in subpopulation AFR AF = 0.000145 (6/41412). AF 95% confidence interval is 0.0000629. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002017.5. 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_002017.5	MANE Select	c.30G>A	p.Ser10Ser	synonymous	Exon 2 of 9	NP_002008.2
	FLI1	NM_001440372.1		c.30G>A	p.Ser10Ser	synonymous	Exon 2 of 7	NP_001427301.1
	FLI1	NM_001167681.3		c.-70G>A		5_prime_UTR	Exon 3 of 10	NP_001161153.1	Q01543-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	ENST00000527786.7	TSL:1 MANE Select	c.30G>A	p.Ser10Ser	synonymous	Exon 2 of 9	ENSP00000433488.2	Q01543-1
	FLI1	ENST00000429175.7	TSL:1	n.30G>A		non_coding_transcript_exon	Exon 2 of 10	ENSP00000399985.3	A0A0A0MSR4
	FLI1	ENST00000897157.1		c.30G>A	p.Ser10Ser	synonymous	Exon 2 of 10	ENSP00000567216.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152136 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000693 AC: 17 AN: 245198 AF XY: 0.0000676

Gnomad AFR exome AF: 0.0000659

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.000501

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000634

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1459962 Hom.: 0 Cov.: 31 AF XY: 0.0000482 AC XY: 35 AN XY: 726072

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.0000449 AC: 2 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 16 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111136

Other (OTH) AF: 0.0000498 AC: 3 AN: 60268

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152136 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74332

African (AFR) AF: 0.000145 AC: 6 AN: 41412

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000119 Hom.: 0

Bravo AF: 0.000121

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.98

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: rs756528214; hg19: chr11-128628021; COSMIC: COSV61384905;