rs17180252

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.5535C>T(p.Leu1845Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 1,609,008 control chromosomes in the GnomAD database, including 4,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 292 hom., cov: 33)

Exomes 𝑓: 0.072 ( 4123 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0500

Publications

10 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=-0.7).

BP6

Variant 14-64772598-G-A is Benign according to our data. Variant chr14-64772598-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.5535C>T	p.Leu1845Leu	synonymous_variant	Exon 26 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.5535C>T	p.Leu1845Leu	synonymous_variant	Exon 26 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5 link	c.1530C>T	p.Leu510Leu	synonymous_variant	Exon 7 of 18	1		ENSP00000451324.1	H0YJE6
SPTB	ENST00000389722.7 link	c.5535C>T	p.Leu1845Leu	synonymous_variant	Exon 25 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.5535C>T	p.Leu1845Leu	synonymous_variant	Exon 26 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8602

AN:

152168

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.0194

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0785

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0833

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0595

AC:

14583

AN:

245264

AF XY:

0.0599

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0410

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.0763

Gnomad NFE exome

AF:

0.0828

Gnomad OTH exome

AF:

0.0596

GnomAD4 exome

AF:

0.0715

AC:

104186

AN:

1456722

Hom.:

4123

Cov.:

AF XY:

0.0708

AC XY:

51303

AN XY:

725100

show subpopulations

African (AFR)

AF:

0.0138

AC:

463

AN:

33472

American (AMR)

AF:

0.0438

AC:

1956

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

1354

AN:

26120

East Asian (EAS)

AF:

0.0168

AC:

665

AN:

39694

South Asian (SAS)

AF:

0.0308

AC:

2655

AN:

86238

European-Finnish (FIN)

AF:

0.0783

AC:

3813

AN:

48714

Middle Eastern (MID)

AF:

0.0381

AC:

214

AN:

5610

European-Non Finnish (NFE)

AF:

0.0802

AC:

89135

AN:

1111860

Other (OTH)

AF:

0.0652

AC:

3931

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6052

12105

18157

24210

30262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3112

6224

9336

12448

15560

<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:

0.0565

AC:

8603

AN:

152286

Hom.:

292

Cov.:

AF XY:

0.0565

AC XY:

4208

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0172

AC:

715

AN:

41576

American (AMR)

AF:

0.0529

AC:

809

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

191

AN:

3472

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5182

South Asian (SAS)

AF:

0.0288

AC:

139

AN:

4826

European-Finnish (FIN)

AF:

0.0785

AC:

833

AN:

10608

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0833

AC:

5662

AN:

67998

Other (OTH)

AF:

0.0440

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

408

816

1225

1633

2041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0725

Hom.:

259

Bravo

AF:

0.0522

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0749

EpiControl

AF:

0.0748

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

-0.70

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.050

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