rs1626923

Variant names:

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.4293A>G(p.Arg1431Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,613,268 control chromosomes in the GnomAD database, including 96,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13942 hom., cov: 31)

Exomes 𝑓: 0.33 ( 82794 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.31

Publications

19 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=-0.55).

BP6

Variant 14-64779905-T-C is Benign according to our data. Variant chr14-64779905-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4293A>G	p.Arg1431Arg	synonymous_variant	Exon 21 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.4293A>G	p.Arg1431Arg	synonymous_variant	Exon 21 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5 link	c.288A>G	p.Arg96Arg	synonymous_variant	Exon 2 of 18	1		ENSP00000451324.1	H0YJE6
SPTB	ENST00000389722.7 link	c.4293A>G	p.Arg1431Arg	synonymous_variant	Exon 20 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.4293A>G	p.Arg1431Arg	synonymous_variant	Exon 21 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61031

AN:

151840

Hom.:

13911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.336

AC:

84212

AN:

250516

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.638

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.364

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.330

AC:

482373

AN:

1461310

Hom.:

82794

Cov.:

AF XY:

0.332

AC XY:

241371

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.645

AC:

21586

AN:

33474

American (AMR)

AF:

0.200

AC:

8958

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8686

AN:

26136

East Asian (EAS)

AF:

0.353

AC:

14011

AN:

39698

South Asian (SAS)

AF:

0.399

AC:

34455

AN:

86254

European-Finnish (FIN)

AF:

0.296

AC:

15792

AN:

53320

Middle Eastern (MID)

AF:

0.342

AC:

1970

AN:

5768

European-Non Finnish (NFE)

AF:

0.320

AC:

355570

AN:

1111572

Other (OTH)

AF:

0.354

AC:

21345

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

18615

37230

55846

74461

93076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.402

AC:

61106

AN:

151958

Hom.:

13942

Cov.:

AF XY:

0.400

AC XY:

29677

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.630

AC:

26082

AN:

41428

American (AMR)

AF:

0.267

AC:

4078

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1143

AN:

3468

East Asian (EAS)

AF:

0.363

AC:

1871

AN:

5160

South Asian (SAS)

AF:

0.412

AC:

1981

AN:

4814

European-Finnish (FIN)

AF:

0.302

AC:

3183

AN:

10552

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21599

AN:

67952

Other (OTH)

AF:

0.374

AC:

790

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1732

3464

5197

6929

8661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.344

Hom.:

21408

Bravo

AF:

0.406

Asia WGS

AF:

0.418

AC:

1456

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.326

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

- -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

-0.55

CADD

Benign

8.4

(source)

DANN

Benign

0.71

PhyloP100

-1.3

Mutation Taster

=97/3

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

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rs1626923

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