NM_001355436.2:c.4860T>C

Variant names:

Variant summary

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

The NM_001355436.2(SPTB):c.4860T>C(p.Ile1620Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,553,578 control chromosomes in the GnomAD database, including 73,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 16309 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57595 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

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=-0.76).

BP6

Variant 14-64774510-A-G is Benign according to our data. Variant chr14-64774510-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64774510-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 24 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 24 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000553938.5 link	c.855T>C	p.Ile285Ile	synonymous_variant	Exon 5 of 18	1		ENSP00000451324.1	H0YJE6
SPTB	ENST00000389722.7 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 23 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.4860T>C	p.Ile1620Ile	synonymous_variant	Exon 24 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62253

AN:

151850

Hom.:

16267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.324

AC:

51720

AN:

159502

Hom.:

9738

AF XY:

0.315

AC XY:

26565

AN XY:

84290

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.270

AC:

378130

AN:

1401610

Hom.:

57595

Cov.:

AF XY:

0.269

AC XY:

186176

AN XY:

691638

show subpopulations

Gnomad4 AFR exome

AF:

0.776

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.489

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.410

AC:

62356

AN:

151968

Hom.:

16309

Cov.:

AF XY:

0.412

AC XY:

30624

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.286

Hom.:

12177

Bravo

AF:

0.430

Asia WGS

AF:

0.414

AC:

1440

AN:

3478

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 22, 2021

GeneDx

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

- -

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

- -

Hereditary spherocytosis type 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: 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

-0.76

CADD

Benign

1.9

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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