Variant X-101349541-CCA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000061.3(BTK):c.*342_*343del 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]

BTK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 72 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
BTK	NM_000061.3 linkuse as main transcript	c.342_343del	3_prime_UTR_variant	19/19	ENST00000308731.8
BTK	NM_001287344.2 linkuse as main transcript	c.342_343del	3_prime_UTR_variant	19/19
BTK	NM_001287345.2 linkuse as main transcript	c.342_343del	3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTK	ENST00000308731.8 linkuse as main transcript	c.342_343del		3_prime_UTR_variant	19/19	1	NM_000061.3	P3	Q06187-1

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

3597

AN:

110595

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

920

AN XY:

32829

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.:

AF XY:

0.0388

AC XY:

1108

AN XY:

28584

show subpopulations

Gnomad4 AFR exome

AF:

0.00779

Gnomad4 AMR exome

AF:

0.0186

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.000171

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0417

Gnomad4 NFE exome

AF:

0.0489

Gnomad4 OTH exome

AF:

0.0361

GnomAD4 genome

AF:

0.0325

AC:

3597

AN:

110646

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

920

AN XY:

32890

show subpopulations

Gnomad4 AFR

AF:

0.00621

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.0212

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00493

Gnomad4 FIN

AF:

0.0452

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0291

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.00438

AC:

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Isolated congenital growth hormone deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over