rs11623956

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001355436.2(SPTB):c.408C>T(p.His136His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,614,004 control chromosomes in the GnomAD database, including 5,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 340 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4945 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.14

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-64803673-G-A is Benign according to our data. Variant chr14-64803673-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.408C>T	p.His136His	synonymous_variant	Exon 4 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SPTB	ENST00000644917.1 link	c.408C>T	p.His136His	synonymous_variant	Exon 4 of 36		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000389722.7 link	c.408C>T	p.His136His	synonymous_variant	Exon 3 of 35	2		ENSP00000374372.3
SPTB	ENST00000389720.4 link	c.408C>T	p.His136His	synonymous_variant	Exon 4 of 32	5		ENSP00000374370.4

Frequencies

GnomAD3 genomes

AF:

0.0592

AC:

8995

AN:

152028

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0475

GnomAD2 exomes

AF:

0.0609

AC:

15316

AN:

251388

AF XY:

0.0621

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0364

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.00484

Gnomad FIN exome

AF:

0.0766

Gnomad NFE exome

AF:

0.0906

Gnomad OTH exome

AF:

0.0614

GnomAD4 exome

AF:

0.0777

AC:

113600

AN:

1461858

Hom.:

4945

Cov.:

AF XY:

0.0770

AC XY:

55962

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0120

AC:

402

AN:

33478

American (AMR)

AF:

0.0390

AC:

1744

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0520

AC:

1359

AN:

26136

East Asian (EAS)

AF:

0.00249

AC:

AN:

39700

South Asian (SAS)

AF:

0.0297

AC:

2564

AN:

86258

European-Finnish (FIN)

AF:

0.0783

AC:

4183

AN:

53418

Middle Eastern (MID)

AF:

0.0451

AC:

260

AN:

5764

European-Non Finnish (NFE)

AF:

0.0890

AC:

99021

AN:

1111984

Other (OTH)

AF:

0.0657

AC:

3968

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

6242

12484

18725

24967

31209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3462

6924

10386

13848

17310

<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:

0.0591

AC:

8992

AN:

152146

Hom.:

340

Cov.:

AF XY:

0.0583

AC XY:

4332

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0153

AC:

637

AN:

41500

American (AMR)

AF:

0.0530

AC:

810

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

183

AN:

3472

East Asian (EAS)

AF:

0.00406

AC:

AN:

5172

South Asian (SAS)

AF:

0.0295

AC:

142

AN:

4820

European-Finnish (FIN)

AF:

0.0779

AC:

825

AN:

10586

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0914

AC:

6214

AN:

67994

Other (OTH)

AF:

0.0470

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

438

875

1313

1750

2188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0720

Hom.:

470

Bravo

AF:

0.0541

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0864

EpiControl

AF:

0.0848

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

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

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

-0.53

CADD

Benign

5.0

(source)

DANN

Benign

0.37

PhyloP100

-1.1

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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