14-64782334-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBA1

The NM_001355436.2(SPTB):c.4222G>C(p.Gly1408Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0625 in 1,614,122 control chromosomes in the GnomAD database, including 3,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 435 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3548 hom. )

Consequence

SPTB
NM_001355436.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.15

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0017653108).

BP6

Variant 14-64782334-C-G is Benign according to our data. Variant chr14-64782334-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 257115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64782334-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4222G>C	p.Gly1408Arg	missense_variant	Exon 20 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.4222G>C	p.Gly1408Arg	missense_variant	Exon 20 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5 link	c.217G>C	p.Gly73Arg	missense_variant	Exon 1 of 18	1		ENSP00000451324.1	H0YJE6
SPTB	ENST00000389722.7 link	c.4222G>C	p.Gly1408Arg	missense_variant	Exon 19 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.4222G>C	p.Gly1408Arg	missense_variant	Exon 20 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9567

AN:

152140

Hom.:

439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0292

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.0961

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0654

AC:

16449

AN:

251426

Hom.:

878

AF XY:

0.0668

AC XY:

9072

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0780

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.0954

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0532

Gnomad OTH exome

AF:

0.0529

GnomAD4 exome

AF:

0.0625

AC:

91323

AN:

1461866

Hom.:

3548

Cov.:

AF XY:

0.0633

AC XY:

46052

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0816

Gnomad4 AMR exome

AF:

0.0237

Gnomad4 ASJ exome

AF:

0.0399

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.0935

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0579

Gnomad4 OTH exome

AF:

0.0659

GnomAD4 genome

AF:

0.0628

AC:

9569

AN:

152256

Hom.:

435

Cov.:

AF XY:

0.0636

AC XY:

4738

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0774

Gnomad4 AMR

AF:

0.0291

Gnomad4 ASJ

AF:

0.0418

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.0959

Gnomad4 FIN

AF:

0.0365

Gnomad4 NFE

AF:

0.0538

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0550

Hom.:

Bravo

AF:

0.0623

TwinsUK

AF:

0.0577

AC:

214

ALSPAC

AF:

0.0649

AC:

250

ESP6500AA

AF:

0.0717

AC:

316

ESP6500EA

AF:

0.0569

AC:

489

ExAC

AF:

0.0675

AC:

8191

Asia WGS

AF:

0.121

AC:

422

AN:

3478

EpiCase

AF:

0.0489

EpiControl

AF:

0.0479

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

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

- -

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

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

.;.;.;T;D;D

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

.;.;D;T;.;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

M;M;M;.;M;M

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.6

D;.;D;D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

D;.;D;D;D;D

Sift4G

Uncertain

0.0030

D;.;D;D;D;D

Polyphen

1.0

.;.;.;.;D;D

Vest4

0.18

MPC

0.83

ClinPred

0.015

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.73

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over