rs56181906

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000542694.2(SPTB):n.347C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,082 control chromosomes in the GnomAD database, including 13,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2991 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10286 hom. )

Consequence

SPTB
ENST00000542694.2 non_coding_transcript_exon

Scores

Splicing: ADA: 0.001358

Clinical Significance

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

Conservation

PhyloP100: 0.00800

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 14-64767867-G-A is Benign according to our data. Variant chr14-64767867-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.6023-8C>T		splice_region_variant, intron_variant	Intron 29 of 35	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1 link	c.6023-8C>T		splice_region_variant, intron_variant	Intron 29 of 35		NM_001355436.2	ENSP00000495909.1		P11277-2

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25226

AN:

151934

Hom.:

2984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.00714

Gnomad SAS

AF:

0.0634

Gnomad FIN

AF:

0.0789

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.142

GnomAD2 exomes

AF:

0.105

AC:

26205

AN:

249694

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.0656

Gnomad ASJ exome

AF:

0.0929

Gnomad EAS exome

AF:

0.00921

Gnomad FIN exome

AF:

0.0825

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.109

AC:

159793

AN:

1461030

Hom.:

10286

Cov.:

AF XY:

0.108

AC XY:

78179

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.345

AC:

11536

AN:

33460

American (AMR)

AF:

0.0708

AC:

3162

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0990

AC:

2587

AN:

26132

East Asian (EAS)

AF:

0.00562

AC:

223

AN:

39690

South Asian (SAS)

AF:

0.0688

AC:

5929

AN:

86220

European-Finnish (FIN)

AF:

0.0858

AC:

4574

AN:

53310

Middle Eastern (MID)

AF:

0.0858

AC:

475

AN:

5536

European-Non Finnish (NFE)

AF:

0.112

AC:

124595

AN:

1111664

Other (OTH)

AF:

0.111

AC:

6712

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7891

15782

23672

31563

39454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4502

9004

13506

18008

22510

<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:

0.166

AC:

25262

AN:

152052

Hom.:

2991

Cov.:

AF XY:

0.161

AC XY:

12003

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.338

AC:

13999

AN:

41422

American (AMR)

AF:

0.100

AC:

1536

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

359

AN:

3462

East Asian (EAS)

AF:

0.00696

AC:

AN:

5172

South Asian (SAS)

AF:

0.0628

AC:

302

AN:

4808

European-Finnish (FIN)

AF:

0.0789

AC:

836

AN:

10602

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7781

AN:

67978

Other (OTH)

AF:

0.141

AC:

298

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

961

1922

2883

3844

4805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.142

Hom.:

900

Bravo

AF:

0.173

Asia WGS

AF:

0.0640

AC:

225

AN:

3478

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.5

(source)

DANN

Benign

0.69

PhyloP100

0.0080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.052

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