dbSNP rs3745516: SPIB:c.340-120A>G (chr19-50423485-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003121.5(SPIB):c.340-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,399,826 control chromosomes in the GnomAD database, including 371,614 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 0.61 ( 31811 hom., cov: 31)

Exomes 𝑓: 0.73 ( 339803 hom. )

Consequence

SPIB
NM_003121.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.215

Publications

55 publications found

Variant links:

Genes affected

SPIB (HGNC:11242): (Spi-B transcription factor) The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5'-GAGGAA-3') and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

SPIB links:

ENSG00000142539 (HGNC:):

ENSG00000142539 links:

Genome browser will be placed here

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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003121.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPIB	NM_003121.5	MANE Select	c.340-120A>G	intron	N/A	NP_003112.2	Q01892-1
SPIB	NM_001244000.2		c.282-155A>G	intron	N/A	NP_001230929.2
SPIB	NM_001243999.2		c.340-120A>G	intron	N/A	NP_001230928.1	Q01892-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPIB	ENST00000595883.6	TSL:1 MANE Select	c.340-120A>G	intron	N/A	ENSP00000471921.1	Q01892-1
ENSG00000142539	ENST00000599632.1	TSL:5	c.742-120A>G	intron	N/A	ENSP00000473233.1	M0R3H8
SPIB	ENST00000270632.7	TSL:1	c.340-120A>G	intron	N/A	ENSP00000270632.7	Q01892-2

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93486

AN:

151982

Hom.:

31806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.649

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.611

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.602

GnomAD4 exome

AF:

0.727

AC:

907238

AN:

1247724

Hom.:

339803

AF XY:

0.725

AC XY:

446919

AN XY:

616306

show subpopulations

African (AFR)

AF:

0.333

AC:

9416

AN:

28310

American (AMR)

AF:

0.662

AC:

19861

AN:

30014

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

12815

AN:

19538

East Asian (EAS)

AF:

0.175

AC:

6534

AN:

37406

South Asian (SAS)

AF:

0.644

AC:

43645

AN:

67810

European-Finnish (FIN)

AF:

0.815

AC:

35888

AN:

44012

Middle Eastern (MID)

AF:

0.633

AC:

3155

AN:

4984

European-Non Finnish (NFE)

AF:

0.768

AC:

740006

AN:

963180

Other (OTH)

AF:

0.685

AC:

35918

AN:

52470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10977

21954

32931

43908

54885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17456

34912

52368

69824

87280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.615

AC:

93530

AN:

152102

Hom.:

31811

Cov.:

AF XY:

0.616

AC XY:

45814

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.345

AC:

14326

AN:

41490

American (AMR)

AF:

0.660

AC:

10097

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.649

AC:

2252

AN:

3472

East Asian (EAS)

AF:

0.205

AC:

1051

AN:

5134

South Asian (SAS)

AF:

0.610

AC:

2942

AN:

4820

European-Finnish (FIN)

AF:

0.832

AC:

8816

AN:

10598

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.763

AC:

51869

AN:

67976

Other (OTH)

AF:

0.605

AC:

1280

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1554

3109

4663

6218

7772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.701

Hom.:

171758

Bravo

AF:

0.588

Asia WGS

AF:

0.428

AC:

1489

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.3

(source)

DANN

Benign

0.34

PhyloP100

0.21

Mutation Taster

=96/4

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over