chr14-64793509-T-G

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.2154A>C(p.Ile718Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,834 control chromosomes in the GnomAD database, including 121,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16184 hom., cov: 32)

Exomes 𝑓: 0.37 ( 105615 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.30

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=-0.8).

BP6

Variant 14-64793509-T-G is Benign according to our data. Variant chr14-64793509-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 257102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64793509-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.2154A>C	p.Ile718Ile	synonymous_variant	Exon 14 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.2154A>C	p.Ile718Ile	synonymous_variant	Exon 14 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
SPTB	ENST00000389722.7 link	c.2154A>C	p.Ile718Ile	synonymous_variant	Exon 13 of 35	2		ENSP00000374372.3	P11277-2
SPTB	ENST00000389720.4 link	c.2154A>C	p.Ile718Ile	synonymous_variant	Exon 14 of 32	5		ENSP00000374370.4	P11277-1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66863

AN:

151936

Hom.:

16156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.378

AC:

94946

AN:

250852

Hom.:

19410

AF XY:

0.384

AC XY:

52141

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.380

GnomAD4 exome

AF:

0.373

AC:

545365

AN:

1461780

Hom.:

105615

Cov.:

AF XY:

0.378

AC XY:

274552

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.664

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.394

GnomAD4 genome

AF:

0.440

AC:

66939

AN:

152054

Hom.:

16184

Cov.:

AF XY:

0.438

AC XY:

32540

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.650

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.504

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.420

Alfa

AF:

0.388

Hom.:

19875

Bravo

AF:

0.446

Asia WGS

AF:

0.407

AC:

1415

AN:

3478

EpiCase

AF:

0.379

EpiControl

AF:

0.385

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Apr 05, 2021

GeneDx

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

-0.80

CADD

Benign

1.2

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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