14-64779238-C-T

Variant names:

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.4482G>A(p.Val1494Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,604,858 control chromosomes in the GnomAD database, including 61,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 11186 hom., cov: 32)

Exomes 𝑓: 0.25 ( 50762 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.432

Publications

18 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=-0.29).

BP6

Variant 14-64779238-C-T is Benign according to our data. Variant chr14-64779238-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.432 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4482G>A	p.Val1494Val	synonymous_variant	Exon 22 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SPTB	ENST00000644917.1 link	c.4482G>A	p.Val1494Val	synonymous_variant	Exon 22 of 36		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000553938.5 link	c.477G>A	p.Val159Val	synonymous_variant	Exon 3 of 18	1		ENSP00000451324.1
SPTB	ENST00000389722.7 link	c.4482G>A	p.Val1494Val	synonymous_variant	Exon 21 of 35	2		ENSP00000374372.3
SPTB	ENST00000389720.4 link	c.4482G>A	p.Val1494Val	synonymous_variant	Exon 22 of 32	5		ENSP00000374370.4

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51788

AN:

151730

Hom.:

11159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.325

GnomAD2 exomes

AF:

0.267

AC:

66453

AN:

248638

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.251

AC:

364781

AN:

1453010

Hom.:

50762

Cov.:

AF XY:

0.254

AC XY:

183546

AN XY:

722990

show subpopulations

African (AFR)

AF:

0.633

AC:

21047

AN:

33234

American (AMR)

AF:

0.145

AC:

6476

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

6942

AN:

26012

East Asian (EAS)

AF:

0.322

AC:

12709

AN:

39522

South Asian (SAS)

AF:

0.366

AC:

31383

AN:

85748

European-Finnish (FIN)

AF:

0.220

AC:

11701

AN:

53210

Middle Eastern (MID)

AF:

0.299

AC:

1716

AN:

5746

European-Non Finnish (NFE)

AF:

0.232

AC:

255833

AN:

1104810

Other (OTH)

AF:

0.282

AC:

16974

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

13544

27089

40633

54178

67722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9000

18000

27000

36000

45000

<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:

0.341

AC:

51853

AN:

151848

Hom.:

11186

Cov.:

AF XY:

0.339

AC XY:

25198

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.613

AC:

25322

AN:

41320

American (AMR)

AF:

0.209

AC:

3185

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

908

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1737

AN:

5152

South Asian (SAS)

AF:

0.380

AC:

1831

AN:

4816

European-Finnish (FIN)

AF:

0.228

AC:

2406

AN:

10572

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15471

AN:

67934

Other (OTH)

AF:

0.321

AC:

676

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1516

3032

4548

6064

7580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.274

Hom.:

20404

Bravo

AF:

0.350

Asia WGS

AF:

0.370

AC:

1287

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 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

-0.29

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

-0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

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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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