Genetic Variant NM_003120.3:c.*330C>T (chr11-47354897-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003120.3(SPI1):c.*330C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 238,742 control chromosomes in the GnomAD database, including 55,669 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 0.69 ( 36049 hom., cov: 29)

Exomes 𝑓: 0.66 ( 19620 hom. )

Consequence

SPI1
NM_003120.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Variant links:

Genes affected

SPI1 (HGNC:11241): (Spi-1 proto-oncogene) This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear protein binds to a purine-rich sequence known as the PU-box found near the promoters of target genes, and regulates their expression in coordination with other transcription factors and cofactors. The protein can also regulate alternative splicing of target genes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SPI1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3 link	c.*330C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000378538.8	NP_003111.2	P17947-1
SPI1	NM_001080547.2 link	c.*330C>T		3_prime_UTR_variant	Exon 5 of 5		NP_001074016.1	P17947-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538.8 link	c.*330C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_003120.3	ENSP00000367799.4		P17947-1

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104420

AN:

151702

Hom.:

36018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.517

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.605

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.665

GnomAD4 exome

AF:

0.665

AC:

57768

AN:

86922

Hom.:

19620

Cov.:

AF XY:

0.665

AC XY:

29461

AN XY:

44302

show subpopulations

African (AFR)

AF:

0.737

AC:

1886

AN:

2558

American (AMR)

AF:

0.619

AC:

1491

AN:

2410

Ashkenazi Jewish (ASJ)

AF:

0.675

AC:

2146

AN:

3178

East Asian (EAS)

AF:

0.636

AC:

4530

AN:

7118

South Asian (SAS)

AF:

0.709

AC:

581

AN:

820

European-Finnish (FIN)

AF:

0.664

AC:

6129

AN:

9232

Middle Eastern (MID)

AF:

0.634

AC:

298

AN:

470

European-Non Finnish (NFE)

AF:

0.666

AC:

36886

AN:

55424

Other (OTH)

AF:

0.669

AC:

3821

AN:

5712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

908

1817

2725

3634

4542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.688

AC:

104495

AN:

151820

Hom.:

36049

Cov.:

AF XY:

0.687

AC XY:

50967

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.746

AC:

30867

AN:

41386

American (AMR)

AF:

0.618

AC:

9432

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

2370

AN:

3470

East Asian (EAS)

AF:

0.696

AC:

3594

AN:

5162

South Asian (SAS)

AF:

0.707

AC:

3403

AN:

4812

European-Finnish (FIN)

AF:

0.686

AC:

7213

AN:

10516

Middle Eastern (MID)

AF:

0.603

AC:

176

AN:

292

European-Non Finnish (NFE)

AF:

0.671

AC:

45582

AN:

67896

Other (OTH)

AF:

0.658

AC:

1390

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1663

3326

4990

6653

8316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.671

Hom.:

59829

Bravo

AF:

0.685

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.0

(source)

DANN

Benign

0.51

PhyloP100

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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NM_003120.3:c.*330C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over