rs3740689

Variant names:

• chr11-47359042-G-A
• rs3740689
• NM_003120.3:c.331-36C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47359042-G-A
• chr11-47359042-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003120.3(SPI1):​c.331-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,506,956 control chromosomes in the GnomAD database, including 240,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (18105 hom., cov: 32)
  • Exomes 𝑓: 0.57 (222333 hom.)
• Consequence: SPI1 NM_003120.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.59
• Publications: 28 publications found

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 Gene-Disease associations (from GenCC):

• agammaglobulinemia 10, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-47359042-G-A is Benign according to our data. Variant chr11-47359042-G-A is described in ClinVar as Benign. ClinVar VariationId is 2687976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3	c.331-36C>T		intron_variant	Intron 3 of 4	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.334-36C>T		intron_variant	Intron 3 of 4		NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538.8	c.331-36C>T		intron_variant	Intron 3 of 4	1	NM_003120.3	ENSP00000367799.4

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68076 AN: 151938 Hom.: 18101 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.521

GnomAD2 exomes AF: 0.516 AC: 77585 AN: 150388 AF XY: 0.530

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.601

Gnomad EAS exome AF: 0.459

Gnomad FIN exome AF: 0.507

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.568

GnomAD4 exome AF: 0.567 AC: 768422 AN: 1354900 Hom.: 222333 Cov.: 38 AF XY: 0.569 AC XY: 377000 AN XY: 662542

African (AFR) AF: 0.132 AC: 3996 AN: 30338

American (AMR) AF: 0.476 AC: 12911 AN: 27096

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 11646 AN: 19536

East Asian (EAS) AF: 0.431 AC: 16599 AN: 38484

South Asian (SAS) AF: 0.579 AC: 39694 AN: 68516

European-Finnish (FIN) AF: 0.513 AC: 24747 AN: 48272

Middle Eastern (MID) AF: 0.557 AC: 2779 AN: 4990

European-Non Finnish (NFE) AF: 0.588 AC: 624883 AN: 1061872

Other (OTH) AF: 0.559 AC: 31167 AN: 55796

GnomAD4 genome AF: 0.448 AC: 68086 AN: 152056 Hom.: 18105 Cov.: 32 AF XY: 0.445 AC XY: 33087 AN XY: 74320

African (AFR) AF: 0.149 AC: 6205 AN: 41520

American (AMR) AF: 0.486 AC: 7427 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2077 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2395 AN: 5148

South Asian (SAS) AF: 0.593 AC: 2855 AN: 4816

European-Finnish (FIN) AF: 0.494 AC: 5229 AN: 10578

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40074 AN: 67930

Other (OTH) AF: 0.528 AC: 1112 AN: 2108

Alfa AF: 0.559 Hom.: 42230

Bravo AF: 0.431

Asia WGS AF: 0.562 AC: 1959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 81% of patients studied by a panel of primary immunodeficiencies. Number of patients: 77. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.64
PhyloP100		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3740689; hg19: chr11-47380593; COSMIC: COSV57045714;