rs2277503

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001355436.2(SPTB):c.177C>T(p.Thr59Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,614,128 control chromosomes in the GnomAD database, including 2,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 231 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2217 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.46

Publications

13 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 14-64805062-G-A is Benign according to our data. Variant chr14-64805062-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.177C>T	p.Thr59Thr	synonymous_variant	Exon 3 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.177C>T	p.Thr59Thr	synonymous_variant	Exon 3 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000389722.7 link	c.177C>T	p.Thr59Thr	synonymous_variant	Exon 2 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.177C>T	p.Thr59Thr	synonymous_variant	Exon 3 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.0465

AC:

7069

AN:

152120

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.0589

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0459

Gnomad OTH

AF:

0.0502

GnomAD2 exomes

AF:

0.0528

AC:

13275

AN:

251452

AF XY:

0.0534

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0439

Gnomad EAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.0319

Gnomad NFE exome

AF:

0.0488

Gnomad OTH exome

AF:

0.0463

GnomAD4 exome

AF:

0.0485

AC:

70889

AN:

1461890

Hom.:

2217

Cov.:

AF XY:

0.0490

AC XY:

35648

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0375

AC:

1257

AN:

33480

American (AMR)

AF:

0.0242

AC:

1082

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0474

AC:

1239

AN:

26136

East Asian (EAS)

AF:

0.157

AC:

6217

AN:

39700

South Asian (SAS)

AF:

0.0559

AC:

4823

AN:

86258

European-Finnish (FIN)

AF:

0.0324

AC:

1733

AN:

53420

Middle Eastern (MID)

AF:

0.0534

AC:

308

AN:

5768

European-Non Finnish (NFE)

AF:

0.0459

AC:

51034

AN:

1112008

Other (OTH)

AF:

0.0529

AC:

3196

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3913

7825

11738

15650

19563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1954

3908

5862

7816

9770

<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:

0.0465

AC:

7075

AN:

152238

Hom.:

231

Cov.:

AF XY:

0.0464

AC XY:

3457

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0375

AC:

1559

AN:

41554

American (AMR)

AF:

0.0340

AC:

520

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

155

AN:

3472

East Asian (EAS)

AF:

0.180

AC:

933

AN:

5172

South Asian (SAS)

AF:

0.0587

AC:

282

AN:

4802

European-Finnish (FIN)

AF:

0.0327

AC:

347

AN:

10610

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0459

AC:

3125

AN:

68014

Other (OTH)

AF:

0.0497

AC:

105

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

341

682

1022

1363

1704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0484

Hom.:

835

Bravo

AF:

0.0471

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

EpiCase

AF:

0.0483

EpiControl

AF:

0.0500

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Jan 29, 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

-0.35

CADD

Benign

9.2

(source)

DANN

Benign

0.69

PhyloP100

3.5

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