rs4899145

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.4818C>T(p.Tyr1606Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 1,613,884 control chromosomes in the GnomAD database, including 4,602 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 ( 296 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4306 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0440

Publications

14 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 14-64775149-G-A is Benign according to our data. Variant chr14-64775149-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.044 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4818C>T	p.Tyr1606Tyr	synonymous_variant	Exon 23 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SPTB	ENST00000644917.1 link	c.4818C>T	p.Tyr1606Tyr	synonymous_variant	Exon 23 of 36		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000553938.5 link	c.813C>T	p.Tyr271Tyr	synonymous_variant	Exon 4 of 18	1		ENSP00000451324.1
SPTB	ENST00000389722.7 link	c.4818C>T	p.Tyr1606Tyr	synonymous_variant	Exon 22 of 35	2		ENSP00000374372.3
SPTB	ENST00000389720.4 link	c.4818C>T	p.Tyr1606Tyr	synonymous_variant	Exon 23 of 32	5		ENSP00000374370.4

Frequencies

GnomAD3 genomes

AF:

0.0585

AC:

8910

AN:

152180

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0536

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0847

Gnomad OTH

AF:

0.0440

GnomAD2 exomes

AF:

0.0607

AC:

15211

AN:

250798

AF XY:

0.0610

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.0411

Gnomad ASJ exome

AF:

0.0505

Gnomad EAS exome

AF:

0.0261

Gnomad FIN exome

AF:

0.0762

Gnomad NFE exome

AF:

0.0842

Gnomad OTH exome

AF:

0.0603

GnomAD4 exome

AF:

0.0731

AC:

106893

AN:

1461586

Hom.:

4306

Cov.:

AF XY:

0.0722

AC XY:

52530

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.0184

AC:

615

AN:

33480

American (AMR)

AF:

0.0440

AC:

1966

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

1355

AN:

26136

East Asian (EAS)

AF:

0.0165

AC:

657

AN:

39700

South Asian (SAS)

AF:

0.0303

AC:

2611

AN:

86258

European-Finnish (FIN)

AF:

0.0786

AC:

4179

AN:

53150

Middle Eastern (MID)

AF:

0.0392

AC:

226

AN:

5768

European-Non Finnish (NFE)

AF:

0.0821

AC:

91282

AN:

1111980

Other (OTH)

AF:

0.0663

AC:

4002

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

6179

12358

18537

24716

30895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3192

6384

9576

12768

15960

<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:

0.0585

AC:

8912

AN:

152298

Hom.:

296

Cov.:

AF XY:

0.0585

AC XY:

4354

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0224

AC:

932

AN:

41568

American (AMR)

AF:

0.0536

AC:

820

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

191

AN:

3470

East Asian (EAS)

AF:

0.0197

AC:

102

AN:

5186

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4822

European-Finnish (FIN)

AF:

0.0767

AC:

814

AN:

10608

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0847

AC:

5763

AN:

68020

Other (OTH)

AF:

0.0440

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

454

908

1363

1817

2271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0740

Hom.:

999

Bravo

AF:

0.0544

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0759

EpiControl

AF:

0.0763

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

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

1.8

(source)

DANN

Benign

0.25

PhyloP100

-0.044

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=99/1

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