rs229587

Positions:

chr14-64796582-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001355436.2(SPTB):c.1316G>A(p.Ser439Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,916 control chromosomes in the GnomAD database, including 107,460 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15118 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92342 hom. )

Consequence

SPTB
NM_001355436.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.524

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.087483E-6).

BP6

Variant 14-64796582-C-T is Benign according to our data. Variant chr14-64796582-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64796582-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2 linkuse as main transcript	c.1316G>A	p.Ser439Asn	missense_variant	11/36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 linkuse as main transcript	c.1316G>A	p.Ser439Asn	missense_variant	11/36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000389722.7 linkuse as main transcript	c.1316G>A	p.Ser439Asn	missense_variant	10/35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 linkuse as main transcript	c.1316G>A	p.Ser439Asn	missense_variant	11/32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64503

AN:

151966

Hom.:

15091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.369

AC:

92811

AN:

251462

Hom.:

18247

AF XY:

0.373

AC XY:

50696

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.643

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.419

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.342

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.348

AC:

509386

AN:

1461832

Hom.:

92342

Cov.:

AF XY:

0.353

AC XY:

256636

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.645

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.474

Gnomad4 FIN exome

AF:

0.324

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.425

AC:

64573

AN:

152084

Hom.:

15118

Cov.:

AF XY:

0.423

AC XY:

31472

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.485

Gnomad4 FIN

AF:

0.330

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.358

Hom.:

25601

Bravo

AF:

0.432

TwinsUK

AF:

0.332

AC:

1232

ALSPAC

AF:

0.325

AC:

1254

ESP6500AA

AF:

0.635

AC:

2796

ESP6500EA

AF:

0.335

AC:

2879

ExAC

AF:

0.380

AC:

46179

Asia WGS

AF:

0.447

AC:

1554

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.354

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Elliptocytosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hereditary spherocytosis type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Spherocytosis, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.8

DANN

Benign

0.76

DEOGEN2

Benign

0.36

.;.;.;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.35

.;.;T;.;T

MetaRNN

Benign

0.0000051

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.80

N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

N;.;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.44

T;.;T;T;T

Sift4G

Benign

0.49

T;.;T;T;T

Polyphen

0.0030

.;.;.;B;B

Vest4

0.017

MPC

0.18

ClinPred

0.016

GERP RS

0.77

Varity_R

0.11

gMVP

0.32

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