NM_001355436.2:c.4860T>C

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.4860T>C(p.Ile1620Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,553,578 control chromosomes in the GnomAD database, including 73,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 16309 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57595 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

Publications

20 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=-0.76).

BP6

Variant 14-64774510-A-G is Benign according to our data. Variant chr14-64774510-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 24 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 24 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5 link	c.855T>C	p.Ile285Ile	synonymous_variant	Exon 5 of 18	1		ENSP00000451324.1	H0YJE6
SPTB	ENST00000389722.7 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 23 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 24 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62253

AN:

151850

Hom.:

16267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.324

AC:

51720

AN:

159502

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.270

AC:

378130

AN:

1401610

Hom.:

57595

Cov.:

AF XY:

0.269

AC XY:

186176

AN XY:

691638

show subpopulations

African (AFR)

AF:

0.776

AC:

24633

AN:

31752

American (AMR)

AF:

0.328

AC:

11831

AN:

36094

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

7131

AN:

25190

East Asian (EAS)

AF:

0.489

AC:

17609

AN:

35998

South Asian (SAS)

AF:

0.298

AC:

23645

AN:

79406

European-Finnish (FIN)

AF:

0.335

AC:

16408

AN:

49008

Middle Eastern (MID)

AF:

0.308

AC:

1754

AN:

5694

European-Non Finnish (NFE)

AF:

0.238

AC:

257171

AN:

1080350

Other (OTH)

AF:

0.309

AC:

17948

AN:

58118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16401

32802

49202

65603

82004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9090

18180

27270

36360

45450

<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:

0.410

AC:

62356

AN:

151968

Hom.:

16309

Cov.:

AF XY:

0.412

AC XY:

30624

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.752

AC:

31163

AN:

41460

American (AMR)

AF:

0.328

AC:

5017

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

966

AN:

3472

East Asian (EAS)

AF:

0.466

AC:

2387

AN:

5126

South Asian (SAS)

AF:

0.314

AC:

1512

AN:

4820

European-Finnish (FIN)

AF:

0.342

AC:

3615

AN:

10564

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16576

AN:

67926

Other (OTH)

AF:

0.376

AC:

794

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1537

3074

4611

6148

7685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.305

Hom.:

29624

Bravo

AF:

0.430

Asia WGS

AF:

0.414

AC:

1440

AN:

3478

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 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 22, 2021

GeneDx

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

- -

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

- -

Hereditary spherocytosis type 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: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

-0.76

CADD

Benign

1.9

(source)

DANN

Benign

0.60

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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