Genetic Variant NM_003121.5:c.*371G>C (chr19-50428707-G-C) – 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.*371G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 240,828 control chromosomes in the GnomAD database, including 12,267 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 0.32 ( 9627 hom., cov: 32)

Exomes 𝑓: 0.22 ( 2640 hom. )

Consequence

SPIB
NM_003121.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.127

Publications

13 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:

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPIB	NM_003121.5 link	c.*371G>C	3_prime_UTR_variant	Exon 6 of 6	ENST00000595883.6	NP_003112.2	Q01892-1A0A024R4I5
SPIB	NM_001244000.2 link	c.*371G>C	3_prime_UTR_variant	Exon 6 of 6		NP_001230929.2	Q01892
SPIB	NM_001243999.2 link	c.*622G>C	3_prime_UTR_variant	Exon 6 of 6		NP_001230928.1	Q01892-2
SPIB	NM_001243998.2 link	c.*371G>C	3_prime_UTR_variant	Exon 5 of 5		NP_001230927.1	Q01892-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPIB	ENST00000595883.6 link	c.*371G>C	3_prime_UTR_variant	Exon 6 of 6	1	NM_003121.5	ENSP00000471921.1	Q01892-1
SPIB	ENST00000270632.7 link	c.*622G>C	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000270632.7	Q01892-2
SPIB	ENST00000439922.6 link	c.*371G>C	3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000391877.2	Q01892-3
SPIB	ENST00000596074.5 link	c.*711G>C	downstream_gene_variant		2		ENSP00000470970.1	M0R037

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48190

AN:

151962

Hom.:

9602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.558

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.318

GnomAD4 exome

AF:

0.222

AC:

19693

AN:

88748

Hom.:

2640

Cov.:

AF XY:

0.223

AC XY:

9948

AN XY:

44642

show subpopulations

African (AFR)

AF:

0.564

AC:

1831

AN:

3248

American (AMR)

AF:

0.290

AC:

738

AN:

2546

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1222

AN:

3554

East Asian (EAS)

AF:

0.126

AC:

934

AN:

7424

South Asian (SAS)

AF:

0.212

AC:

402

AN:

1892

European-Finnish (FIN)

AF:

0.148

AC:

772

AN:

5204

Middle Eastern (MID)

AF:

0.350

AC:

161

AN:

460

European-Non Finnish (NFE)

AF:

0.207

AC:

12035

AN:

58176

Other (OTH)

AF:

0.256

AC:

1598

AN:

6244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

699

1399

2098

2798

3497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.317

AC:

48258

AN:

152080

Hom.:

9627

Cov.:

AF XY:

0.311

AC XY:

23159

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.558

AC:

23137

AN:

41450

American (AMR)

AF:

0.304

AC:

4653

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1203

AN:

3468

East Asian (EAS)

AF:

0.166

AC:

857

AN:

5174

South Asian (SAS)

AF:

0.254

AC:

1226

AN:

4822

European-Finnish (FIN)

AF:

0.160

AC:

1693

AN:

10596

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.213

AC:

14464

AN:

67970

Other (OTH)

AF:

0.317

AC:

669

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1500

3000

4500

6000

7500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.280

Hom.:

925

Bravo

AF:

0.336

Asia WGS

AF:

0.253

AC:

879

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.5

(source)

DANN

Benign

0.65

PhyloP100

-0.13

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over