Variant rs11623956 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001355436.2(SPTB):c.408C>T(p.His136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,614,004 control chromosomes in the GnomAD database, including 5,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 340 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4945 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.14

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-64803673-G-A is Benign according to our data. Variant chr14-64803673-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64803673-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTB	NM_001355436.2 linkuse as main transcript	c.408C>T	p.His136=	synonymous_variant	4/36	ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTB	ENST00000644917.1 linkuse as main transcript	c.408C>T	p.His136=	synonymous_variant	4/36		NM_001355436.2	P1	P11277-2
SPTB	ENST00000389722.7 linkuse as main transcript	c.408C>T	p.His136=	synonymous_variant	3/35	2		P1	P11277-2
SPTB	ENST00000389720.4 linkuse as main transcript	c.408C>T	p.His136=	synonymous_variant	4/32	5			P11277-1

Frequencies

GnomAD3 genomes

AF:

0.0592

AC:

8995

AN:

152028

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0475

GnomAD3 exomes

AF:

0.0609

AC:

15316

AN:

251388

Hom.:

616

AF XY:

0.0621

AC XY:

8437

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0364

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.00484

Gnomad SAS exome

AF:

0.0298

Gnomad FIN exome

AF:

0.0766

Gnomad NFE exome

AF:

0.0906

Gnomad OTH exome

AF:

0.0614

GnomAD4 exome

AF:

0.0777

AC:

113600

AN:

1461858

Hom.:

4945

Cov.:

AF XY:

0.0770

AC XY:

55962

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.0390

Gnomad4 ASJ exome

AF:

0.0520

Gnomad4 EAS exome

AF:

0.00249

Gnomad4 SAS exome

AF:

0.0297

Gnomad4 FIN exome

AF:

0.0783

Gnomad4 NFE exome

AF:

0.0890

Gnomad4 OTH exome

AF:

0.0657

GnomAD4 genome

AF:

0.0591

AC:

8992

AN:

152146

Hom.:

340

Cov.:

AF XY:

0.0583

AC XY:

4332

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.0530

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.00406

Gnomad4 SAS

AF:

0.0295

Gnomad4 FIN

AF:

0.0779

Gnomad4 NFE

AF:

0.0914

Gnomad4 OTH

AF:

0.0470

Alfa

AF:

0.0721

Hom.:

357

Bravo

AF:

0.0541

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0864

EpiControl

AF:

0.0848

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.0

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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