14-64793101-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001355436.2(SPTB):​c.2562C>T​(p.Phe854Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,614,076 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 18 hom. )

Consequence

SPTB
NM_001355436.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0190

Publications

2 publications found
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 Gene-Disease associations (from GenCC):
  • hereditary spherocytosis type 2
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • elliptocytosis 3
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • hereditary elliptocytosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hereditary spherocytosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 14-64793101-G-A is Benign according to our data. Variant chr14-64793101-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.019 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00163 (248/152316) while in subpopulation EAS AF = 0.0168 (87/5176). AF 95% confidence interval is 0.014. There are 2 homozygotes in GnomAd4. There are 127 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPTBNM_001355436.2 linkc.2562C>T p.Phe854Phe synonymous_variant Exon 14 of 36 ENST00000644917.1 NP_001342365.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPTBENST00000644917.1 linkc.2562C>T p.Phe854Phe synonymous_variant Exon 14 of 36 NM_001355436.2 ENSP00000495909.1 P11277-2
SPTBENST00000389722.7 linkc.2562C>T p.Phe854Phe synonymous_variant Exon 13 of 35 2 ENSP00000374372.3 P11277-2
SPTBENST00000389720.4 linkc.2562C>T p.Phe854Phe synonymous_variant Exon 14 of 32 5 ENSP00000374370.4 P11277-1

Frequencies

GnomAD3 genomes
AF:
0.00157
AC:
239
AN:
152198
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00530
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0168
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00191
GnomAD2 exomes
AF:
0.00289
AC:
725
AN:
251054
AF XY:
0.00237
show subpopulations
Gnomad AFR exome
AF:
0.000928
Gnomad AMR exome
AF:
0.00925
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0189
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000793
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00110
AC:
1606
AN:
1461760
Hom.:
18
Cov.:
32
AF XY:
0.00108
AC XY:
784
AN XY:
727178
show subpopulations
African (AFR)
AF:
0.00146
AC:
49
AN:
33480
American (AMR)
AF:
0.00968
AC:
433
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0175
AC:
695
AN:
39700
South Asian (SAS)
AF:
0.000649
AC:
56
AN:
86258
European-Finnish (FIN)
AF:
0.0000375
AC:
2
AN:
53286
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000135
AC:
150
AN:
1112012
Other (OTH)
AF:
0.00366
AC:
221
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
116
231
347
462
578
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
28
56
84
112
140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00163
AC:
248
AN:
152316
Hom.:
2
Cov.:
32
AF XY:
0.00171
AC XY:
127
AN XY:
74470
show subpopulations
African (AFR)
AF:
0.00118
AC:
49
AN:
41574
American (AMR)
AF:
0.00536
AC:
82
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.0168
AC:
87
AN:
5176
South Asian (SAS)
AF:
0.00166
AC:
8
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000147
AC:
10
AN:
68032
Other (OTH)
AF:
0.00568
AC:
12
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
13
26
38
51
64
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00120
Hom.:
2
Bravo
AF:
0.00223
Asia WGS
AF:
0.0300
AC:
104
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Nov 25, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
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

- -

Dec 03, 2024
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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
3.1
DANN
Benign
0.67
PhyloP100
0.019
Mutation Taster
=99/1
polymorphism

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

Other links and lift over

dbSNP: rs12433436; hg19: chr14-65259819; COSMIC: COSV101072303; API