rs230703

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001355436.2(SPTB):c.876+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,612,972 control chromosomes in the GnomAD database, including 84,087 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11223 hom., cov: 33)

Exomes 𝑓: 0.31 ( 72864 hom. )

Consequence

SPTB
NM_001355436.2 splice_region, intron

Scores

Splicing: ADA: 0.00007788

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.737

Publications

16 publications found

Variant links:

Genes affected

SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

SPTB Gene-Disease associations (from GenCC):

hereditary spherocytosis type 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
elliptocytosis 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spherocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-64800751-T-C is Benign according to our data. Variant chr14-64800751-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.876+5A>G		splice_region_variant, intron_variant	Intron 8 of 35	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.876+5A>G	splice_region_variant, intron_variant	Intron 8 of 35		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000389722.7 link	c.876+5A>G	splice_region_variant, intron_variant	Intron 7 of 34	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.876+5A>G	splice_region_variant, intron_variant	Intron 8 of 31	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55582

AN:

151960

Hom.:

11207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.363

GnomAD2 exomes

AF:

0.316

AC:

79366

AN:

251104

AF XY:

0.322

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.309

AC:

452024

AN:

1460894

Hom.:

72864

Cov.:

AF XY:

0.313

AC XY:

227847

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.541

AC:

18103

AN:

33468

American (AMR)

AF:

0.242

AC:

10828

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

9869

AN:

26132

East Asian (EAS)

AF:

0.162

AC:

6418

AN:

39690

South Asian (SAS)

AF:

0.425

AC:

36682

AN:

86232

European-Finnish (FIN)

AF:

0.302

AC:

16105

AN:

53408

Middle Eastern (MID)

AF:

0.383

AC:

2202

AN:

5752

European-Non Finnish (NFE)

AF:

0.299

AC:

332154

AN:

1111154

Other (OTH)

AF:

0.326

AC:

19663

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

15857

31714

47571

63428

79285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10968

21936

32904

43872

54840

<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:

0.366

AC:

55624

AN:

152078

Hom.:

11223

Cov.:

AF XY:

0.364

AC XY:

27064

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.530

AC:

21984

AN:

41478

American (AMR)

AF:

0.293

AC:

4475

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1278

AN:

3468

East Asian (EAS)

AF:

0.153

AC:

790

AN:

5164

South Asian (SAS)

AF:

0.431

AC:

2077

AN:

4814

European-Finnish (FIN)

AF:

0.307

AC:

3254

AN:

10584

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20546

AN:

67966

Other (OTH)

AF:

0.358

AC:

757

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1737

3473

5210

6946

8683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.330

Hom.:

28776

Bravo

AF:

0.368

Asia WGS

AF:

0.322

AC:

1121

AN:

3478

EpiCase

AF:

0.317

EpiControl

AF:

0.317

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 18, 2022

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Elliptocytosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spherocytosis type 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spherocytosis, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.8

(source)

DANN

Benign

0.54

PhyloP100

-0.74

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000078

dbscSNV1_RF

Benign

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over