14-64779905-T-C

Variant summary

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

The NM_001355436.2(SPTB):ā€‹c.4293A>Gā€‹(p.Arg1431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,613,268 control chromosomes in the GnomAD database, including 96,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.40 ( 13942 hom., cov: 31)
Exomes š‘“: 0.33 ( 82794 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.31
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 14-64779905-T-C is Benign according to our data. Variant chr14-64779905-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64779905-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.31 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPTBNM_001355436.2 linkuse as main transcriptc.4293A>G p.Arg1431= synonymous_variant 21/36 ENST00000644917.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPTBENST00000644917.1 linkuse as main transcriptc.4293A>G p.Arg1431= synonymous_variant 21/36 NM_001355436.2 P1P11277-2
SPTBENST00000553938.5 linkuse as main transcriptc.288A>G p.Arg96= synonymous_variant 2/181
SPTBENST00000389722.7 linkuse as main transcriptc.4293A>G p.Arg1431= synonymous_variant 20/352 P1P11277-2
SPTBENST00000389720.4 linkuse as main transcriptc.4293A>G p.Arg1431= synonymous_variant 21/325 P11277-1

Frequencies

GnomAD3 genomes
AF:
0.402
AC:
61031
AN:
151840
Hom.:
13911
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.629
Gnomad AMI
AF:
0.297
Gnomad AMR
AF:
0.267
Gnomad ASJ
AF:
0.330
Gnomad EAS
AF:
0.364
Gnomad SAS
AF:
0.412
Gnomad FIN
AF:
0.302
Gnomad MID
AF:
0.358
Gnomad NFE
AF:
0.318
Gnomad OTH
AF:
0.373
GnomAD3 exomes
AF:
0.336
AC:
84212
AN:
250516
Hom.:
15509
AF XY:
0.339
AC XY:
45864
AN XY:
135434
show subpopulations
Gnomad AFR exome
AF:
0.638
Gnomad AMR exome
AF:
0.190
Gnomad ASJ exome
AF:
0.327
Gnomad EAS exome
AF:
0.364
Gnomad SAS exome
AF:
0.409
Gnomad FIN exome
AF:
0.299
Gnomad NFE exome
AF:
0.322
Gnomad OTH exome
AF:
0.328
GnomAD4 exome
AF:
0.330
AC:
482373
AN:
1461310
Hom.:
82794
Cov.:
45
AF XY:
0.332
AC XY:
241371
AN XY:
726948
show subpopulations
Gnomad4 AFR exome
AF:
0.645
Gnomad4 AMR exome
AF:
0.200
Gnomad4 ASJ exome
AF:
0.332
Gnomad4 EAS exome
AF:
0.353
Gnomad4 SAS exome
AF:
0.399
Gnomad4 FIN exome
AF:
0.296
Gnomad4 NFE exome
AF:
0.320
Gnomad4 OTH exome
AF:
0.354
GnomAD4 genome
AF:
0.402
AC:
61106
AN:
151958
Hom.:
13942
Cov.:
31
AF XY:
0.400
AC XY:
29677
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.630
Gnomad4 AMR
AF:
0.267
Gnomad4 ASJ
AF:
0.330
Gnomad4 EAS
AF:
0.363
Gnomad4 SAS
AF:
0.412
Gnomad4 FIN
AF:
0.302
Gnomad4 NFE
AF:
0.318
Gnomad4 OTH
AF:
0.374
Alfa
AF:
0.337
Hom.:
15595
Bravo
AF:
0.406
Asia WGS
AF:
0.418
AC:
1456
AN:
3478
EpiCase
AF:
0.323
EpiControl
AF:
0.326

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 30, 2023- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Elliptocytosis Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Spherocytosis, Dominant Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Hereditary spherocytosis type 2 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
8.4
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs1626923; hg19: chr14-65246623; COSMIC: COSV67633848; API