X-101349541-CCA-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_000061.3(BTK):c.*342_*343delTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 226,054 control chromosomes in the GnomAD database, including 152 homozygotes. There are 2,028 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.033 ( 72 hom., 920 hem., cov: 21)
Exomes 𝑓: 0.037 ( 80 hom. 1108 hem. )
Consequence
BTK
NM_000061.3 3_prime_UTR
NM_000061.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.224
Genes affected
BTK (HGNC:1133): (Bruton tyrosine kinase) The protein encoded by this gene plays a crucial role in B-cell development. Mutations in this gene cause X-linked agammaglobulinemia type 1, which is an immunodeficiency characterized by the failure to produce mature B lymphocytes, and associated with a failure of Ig heavy chain rearrangement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP6
Variant X-101349541-CCA-C is Benign according to our data. Variant chrX-101349541-CCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 367690.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0325 (3597/110646) while in subpopulation NFE AF = 0.051 (2697/52855). AF 95% confidence interval is 0.0494. There are 72 homozygotes in GnomAd4. There are 920 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 72 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BTK | NM_000061.3 | c.*342_*343delTG | 3_prime_UTR_variant | Exon 19 of 19 | ENST00000308731.8 | NP_000052.1 | ||
BTK | NM_001287344.2 | c.*342_*343delTG | 3_prime_UTR_variant | Exon 19 of 19 | NP_001274273.1 | |||
BTK | NM_001287345.2 | c.*342_*343delTG | 3_prime_UTR_variant | Exon 17 of 17 | NP_001274274.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0325 AC: 3597AN: 110595Hom.: 72 Cov.: 21 show subpopulations
GnomAD3 genomes
AF:
AC:
3597
AN:
110595
Hom.:
Cov.:
21
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:
GnomAD4 exome AF: 0.0374 AC: 4312AN: 115408Hom.: 80 AF XY: 0.0388 AC XY: 1108AN XY: 28584 show subpopulations
GnomAD4 exome
AF:
AC:
4312
AN:
115408
Hom.:
AF XY:
AC XY:
1108
AN XY:
28584
Gnomad4 AFR exome
AF:
AC:
37
AN:
4750
Gnomad4 AMR exome
AF:
AC:
95
AN:
5100
Gnomad4 ASJ exome
AF:
AC:
116
AN:
4789
Gnomad4 EAS exome
AF:
AC:
2
AN:
11715
Gnomad4 SAS exome
AF:
AC:
37
AN:
3570
Gnomad4 FIN exome
AF:
AC:
149
AN:
3572
Gnomad4 NFE exome
AF:
AC:
3571
AN:
72997
Gnomad4 Remaining exome
AF:
AC:
303
AN:
8382
Heterozygous variant carriers
0
147
294
440
587
734
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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: 0.0325 AC: 3597AN: 110646Hom.: 72 Cov.: 21 AF XY: 0.0280 AC XY: 920AN XY: 32890 show subpopulations
GnomAD4 genome
AF:
AC:
3597
AN:
110646
Hom.:
Cov.:
21
AF XY:
AC XY:
920
AN XY:
32890
Gnomad4 AFR
AF:
AC:
0.00621302
AN:
0.00621302
Gnomad4 AMR
AF:
AC:
0.023904
AN:
0.023904
Gnomad4 ASJ
AF:
AC:
0.0212121
AN:
0.0212121
Gnomad4 EAS
AF:
AC:
0
AN:
0
Gnomad4 SAS
AF:
AC:
0.00492798
AN:
0.00492798
Gnomad4 FIN
AF:
AC:
0.0452279
AN:
0.0452279
Gnomad4 NFE
AF:
AC:
0.0510264
AN:
0.0510264
Gnomad4 OTH
AF:
AC:
0.0291198
AN:
0.0291198
Heterozygous variant carriers
0
129
258
387
516
645
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
38
76
114
152
190
<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:
11
AN:
2522
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked agammaglobulinemia Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Isolated congenital growth hormone deficiency 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
Mutation Taster
=100/0
polymorphism (auto)
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