rs77806

Positions:

Variant summary

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

The NM_001355436.2(SPTB):c.3451A>G(p.Asn1151Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,172 control chromosomes in the GnomAD database, including 87,659 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 0.38 ( 12928 hom., cov: 32)

Exomes 𝑓: 0.31 ( 74731 hom. )

Consequence

SPTB
NM_001355436.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.678

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=8.120305E-6).

BP6

Variant 14-64786514-T-C is Benign according to our data. Variant chr14-64786514-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64786514-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 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.3451A>G	p.Asn1151Asp	missense_variant	16/36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1 linkuse as main transcript	c.3451A>G	p.Asn1151Asp	missense_variant	16/36		NM_001355436.2	ENSP00000495909	P1	P11277-2
SPTB	ENST00000389722.7 linkuse as main transcript	c.3451A>G	p.Asn1151Asp	missense_variant	15/35	2		ENSP00000374372	P1	P11277-2
SPTB	ENST00000389720.4 linkuse as main transcript	c.3451A>G	p.Asn1151Asp	missense_variant	16/32	5		ENSP00000374370		P11277-1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58414

AN:

151888

Hom.:

12909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.358

GnomAD3 exomes

AF:

0.322

AC:

80430

AN:

249892

Hom.:

14287

AF XY:

0.324

AC XY:

43856

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.347

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.313

AC:

457397

AN:

1461166

Hom.:

74731

Cov.:

AF XY:

0.315

AC XY:

229213

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.629

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.314

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.385

AC:

58464

AN:

152006

Hom.:

12928

Cov.:

AF XY:

0.383

AC XY:

28421

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.612

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.315

Hom.:

3184

Bravo

AF:

0.388

TwinsUK

AF:

0.306

AC:

1135

ALSPAC

AF:

0.314

AC:

1209

ESP6500AA

AF:

0.606

AC:

2669

ESP6500EA

AF:

0.301

AC:

2591

ExAC

AF:

0.334

AC:

40511

Asia WGS

AF:

0.388

AC:

1351

AN:

3478

EpiCase

AF:

0.304

EpiControl

AF:

0.311

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	GeneDx	Nov 12, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

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

- -

Spherocytosis, Dominant

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.26

.;.;.;T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.36

.;.;T;.;T

MetaRNN

Benign

0.0000081

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.81

N;N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.12

N;.;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.46

T;.;T;T;T

Sift4G

Benign

0.44

T;.;T;T;T

Polyphen

0.0

.;.;.;B;B

Vest4

0.028

MPC

0.22

ClinPred

0.00026

GERP RS

4.9

Varity_R

0.055

gMVP

0.076

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