rs77806

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3451A>G(p.Asn1151Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,172 control chromosomes in the GnomAD database, including 87,659 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12928 hom., cov: 32)

Exomes 𝑓: 0.31 ( 74731 hom. )

Consequence

SPTB
NM_001355436.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.678

Publications

26 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 (MetaRNN=8.120305E-6).

BP6

Variant 14-64786514-T-C is Benign according to our data. Variant chr14-64786514-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.3451A>G	p.Asn1151Asp	missense_variant	Exon 16 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.3451A>G	p.Asn1151Asp	missense_variant	Exon 16 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000389722.7 link	c.3451A>G	p.Asn1151Asp	missense_variant	Exon 15 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.3451A>G	p.Asn1151Asp	missense_variant	Exon 16 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58414

AN:

151888

Hom.:

12909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.358

GnomAD2 exomes

AF:

0.322

AC:

80430

AN:

249892

AF XY:

0.324

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.347

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.313

AC:

457397

AN:

1461166

Hom.:

74731

Cov.:

AF XY:

0.315

AC XY:

229213

AN XY:

726882

show subpopulations

African (AFR)

AF:

0.629

AC:

21044

AN:

33478

American (AMR)

AF:

0.183

AC:

8146

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

8201

AN:

26134

East Asian (EAS)

AF:

0.337

AC:

13352

AN:

39642

South Asian (SAS)

AF:

0.394

AC:

34019

AN:

86238

European-Finnish (FIN)

AF:

0.282

AC:

14972

AN:

53146

Middle Eastern (MID)

AF:

0.317

AC:

1822

AN:

5742

European-Non Finnish (NFE)

AF:

0.302

AC:

335635

AN:

1111828

Other (OTH)

AF:

0.335

AC:

20206

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

21219

42438

63658

84877

106096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11184

22368

33552

44736

55920

<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:

0.385

AC:

58464

AN:

152006

Hom.:

12928

Cov.:

AF XY:

0.383

AC XY:

28421

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.612

AC:

25379

AN:

41458

American (AMR)

AF:

0.249

AC:

3805

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1074

AN:

3464

East Asian (EAS)

AF:

0.349

AC:

1797

AN:

5148

South Asian (SAS)

AF:

0.404

AC:

1948

AN:

4818

European-Finnish (FIN)

AF:

0.286

AC:

3024

AN:

10568

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20318

AN:

67964

Other (OTH)

AF:

0.355

AC:

749

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1722

3443

5165

6886

8608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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.:

6518

Bravo

AF:

0.388

TwinsUK

AF:

0.306

AC:

1135

ALSPAC

AF:

0.314

AC:

1209

ESP6500AA

AF:

0.606

AC:

2669

ESP6500EA

AF:

0.301

AC:

2591

ExAC

AF:

0.334

AC:

40511

Asia WGS

AF:

0.388

AC:

1351

AN:

3478

EpiCase

AF:

0.304

EpiControl

AF:

0.311

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

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 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 26, 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

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.26

.;.;.;T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.36

.;.;T;.;T

MetaRNN

Benign

0.0000081

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.81

N;N;N;N;N

PhyloP100

0.68

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.12

N;.;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.46

T;.;T;T;T

Sift4G

Benign

0.44

T;.;T;T;T

Polyphen

0.0

.;.;.;B;B

Vest4

0.028

MPC

0.22

ClinPred

0.00026

GERP RS

4.9

Varity_R

0.055

gMVP

0.076

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over