14-64801382-A-G

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.666T>C(p.Phe222Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,614,164 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 74 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 239 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.374

Publications

4 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=-0.58).

BP6

Variant 14-64801382-A-G is Benign according to our data. Variant chr14-64801382-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.374 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.666T>C	p.Phe222Phe	synonymous_variant	Exon 7 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SPTB	ENST00000644917.1 link	c.666T>C	p.Phe222Phe	synonymous_variant	Exon 7 of 36		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000389722.7 link	c.666T>C	p.Phe222Phe	synonymous_variant	Exon 6 of 35	2		ENSP00000374372.3
SPTB	ENST00000389720.4 link	c.666T>C	p.Phe222Phe	synonymous_variant	Exon 7 of 32	5		ENSP00000374370.4

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2925

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0324

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0185

AC:

4653

AN:

251442

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.0625

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0234

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.00742

AC:

10843

AN:

1461816

Hom.:

239

Cov.:

AF XY:

0.00758

AC XY:

5511

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0451

AC:

1511

AN:

33472

American (AMR)

AF:

0.0619

AC:

2767

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0270

AC:

705

AN:

26134

East Asian (EAS)

AF:

0.0349

AC:

1387

AN:

39696

South Asian (SAS)

AF:

0.0259

AC:

2237

AN:

86252

European-Finnish (FIN)

AF:

0.000880

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00137

AC:

1528

AN:

1111978

Other (OTH)

AF:

0.0105

AC:

634

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

695

1390

2085

2780

3475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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:

0.0192

AC:

2930

AN:

152348

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1431

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0429

AC:

1785

AN:

41574

American (AMR)

AF:

0.0400

AC:

612

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3472

East Asian (EAS)

AF:

0.0326

AC:

169

AN:

5180

South Asian (SAS)

AF:

0.0236

AC:

114

AN:

4832

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00179

AC:

122

AN:

68034

Other (OTH)

AF:

0.0222

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0104

Hom.:

Bravo

AF:

0.0253

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00213

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

Nov 14, 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

Jan 29, 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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.4

(source)

DANN

Benign

0.74

PhyloP100

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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