X-101349541-CCA-C

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.224
Variant links:
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]

Genome browser will be placed here

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
BTKNM_000061.3 linkc.*342_*343delTG 3_prime_UTR_variant Exon 19 of 19 ENST00000308731.8 NP_000052.1 Q06187-1Q5JY90
BTKNM_001287344.2 linkc.*342_*343delTG 3_prime_UTR_variant Exon 19 of 19 NP_001274273.1 Q06187-2
BTKNM_001287345.2 linkc.*342_*343delTG 3_prime_UTR_variant Exon 17 of 17 NP_001274274.1 Q06187Q5JY90

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTKENST00000308731 linkc.*342_*343delTG 3_prime_UTR_variant Exon 19 of 19 1 NM_000061.3 ENSP00000308176.8 Q06187-1

Frequencies

GnomAD3 genomes
AF:
0.0325
AC:
3597
AN:
110595
Hom.:
72
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.00623
Gnomad AMI
AF:
0.128
Gnomad AMR
AF:
0.0239
Gnomad ASJ
AF:
0.0212
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00491
Gnomad FIN
AF:
0.0452
Gnomad MID
AF:
0.00431
Gnomad NFE
AF:
0.0510
Gnomad OTH
AF:
0.0295
GnomAD4 exome
AF:
0.0374
AC:
4312
AN:
115408
Hom.:
80
AF XY:
0.0388
AC XY:
1108
AN XY:
28584
show subpopulations
Gnomad4 AFR exome
AF:
0.00779
AC:
37
AN:
4750
Gnomad4 AMR exome
AF:
0.0186
AC:
95
AN:
5100
Gnomad4 ASJ exome
AF:
0.0242
AC:
116
AN:
4789
Gnomad4 EAS exome
AF:
0.000171
AC:
2
AN:
11715
Gnomad4 SAS exome
AF:
0.0104
AC:
37
AN:
3570
Gnomad4 FIN exome
AF:
0.0417
AC:
149
AN:
3572
Gnomad4 NFE exome
AF:
0.0489
AC:
3571
AN:
72997
Gnomad4 Remaining exome
AF:
0.0361
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:
3597
AN:
110646
Hom.:
72
Cov.:
21
AF XY:
0.0280
AC XY:
920
AN XY:
32890
show subpopulations
Gnomad4 AFR
AF:
0.00621
AC:
0.00621302
AN:
0.00621302
Gnomad4 AMR
AF:
0.0239
AC:
0.023904
AN:
0.023904
Gnomad4 ASJ
AF:
0.0212
AC:
0.0212121
AN:
0.0212121
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00493
AC:
0.00492798
AN:
0.00492798
Gnomad4 FIN
AF:
0.0452
AC:
0.0452279
AN:
0.0452279
Gnomad4 NFE
AF:
0.0510
AC:
0.0510264
AN:
0.0510264
Gnomad4 OTH
AF:
0.0291
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:
0.0135
Hom.:
61
Bravo
AF:
0.0302
Asia WGS
AF:
0.00438
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Mutation Taster
=100/0
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs200445244; hg19: chrX-100604529; API