NM_001355436.2:c.2562C>T
Variant names:
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
NM_001355436.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0190
Publications
2 publications found
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 2Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- elliptocytosis 3Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- hereditary elliptocytosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary spherocytosisInheritance: 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 |
---|---|---|---|---|---|---|---|---|
SPTB | NM_001355436.2 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
SPTB | ENST00000644917.1 | c.2562C>T | p.Phe854Phe | synonymous_variant | Exon 14 of 36 | NM_001355436.2 | ENSP00000495909.1 | |||
SPTB | ENST00000389722.7 | c.2562C>T | p.Phe854Phe | synonymous_variant | Exon 13 of 35 | 2 | ENSP00000374372.3 | |||
SPTB | ENST00000389720.4 | c.2562C>T | p.Phe854Phe | synonymous_variant | Exon 14 of 32 | 5 | ENSP00000374370.4 |
Frequencies
GnomAD3 genomes AF: 0.00157 AC: 239AN: 152198Hom.: 1 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
239
AN:
152198
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00289 AC: 725AN: 251054 AF XY: 0.00237 show subpopulations
GnomAD2 exomes
AF:
AC:
725
AN:
251054
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00110 AC: 1606AN: 1461760Hom.: 18 Cov.: 32 AF XY: 0.00108 AC XY: 784AN XY: 727178 show subpopulations
GnomAD4 exome
AF:
AC:
1606
AN:
1461760
Hom.:
Cov.:
32
AF XY:
AC XY:
784
AN XY:
727178
show subpopulations
African (AFR)
AF:
AC:
49
AN:
33480
American (AMR)
AF:
AC:
433
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
695
AN:
39700
South Asian (SAS)
AF:
AC:
56
AN:
86258
European-Finnish (FIN)
AF:
AC:
2
AN:
53286
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
150
AN:
1112012
Other (OTH)
AF:
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: 248AN: 152316Hom.: 2 Cov.: 32 AF XY: 0.00171 AC XY: 127AN XY: 74470 show subpopulations
GnomAD4 genome
AF:
AC:
248
AN:
152316
Hom.:
Cov.:
32
AF XY:
AC XY:
127
AN XY:
74470
show subpopulations
African (AFR)
AF:
AC:
49
AN:
41574
American (AMR)
AF:
AC:
82
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
87
AN:
5176
South Asian (SAS)
AF:
AC:
8
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
10
AN:
68032
Other (OTH)
AF:
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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
104
AN:
3478
EpiCase
AF:
EpiControl
AF:
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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