rs229581

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001355436.2(SPTB):c.300+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,613,542 control chromosomes in the GnomAD database, including 101,038 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14818 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86220 hom. )

Consequence

SPTB
NM_001355436.2 splice_region, intron

Scores

Splicing: ADA: 0.00003127

Clinical Significance

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

Conservation

PhyloP100: 0.457

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 (BayesDel_noAF=-0.91).

BP6

Variant 14-64804932-A-G is Benign according to our data. Variant chr14-64804932-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64804932-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.300+7T>C		splice_region_variant, intron_variant	Intron 3 of 35	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.300+7T>C	splice_region_variant, intron_variant	Intron 3 of 35		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000389722.7 link	c.300+7T>C	splice_region_variant, intron_variant	Intron 2 of 34	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.300+7T>C	splice_region_variant, intron_variant	Intron 3 of 31	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63420

AN:

151970

Hom.:

14792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.359

AC:

89866

AN:

250250

Hom.:

17324

AF XY:

0.363

AC XY:

49126

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.336

AC:

490788

AN:

1461454

Hom.:

86220

Cov.:

AF XY:

0.341

AC XY:

247739

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.650

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.395

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.364

GnomAD4 genome

AF:

0.417

AC:

63488

AN:

152088

Hom.:

14818

Cov.:

AF XY:

0.416

AC XY:

30947

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.364

Hom.:

4773

Bravo

AF:

0.424

Asia WGS

AF:

0.446

AC:

1551

AN:

3478

EpiCase

AF:

0.337

EpiControl

AF:

0.338

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

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 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

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

-0.91

CADD

Benign

6.8

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.090

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