Variant rs148358153 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000061.3(BTK):c.531T>C(p.Pro177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,210,264 control chromosomes in the GnomAD database, including 10 homozygotes. There are 432 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 7 hom., 218 hem., cov: 23)

Exomes 𝑓: 0.00067 ( 3 hom. 214 hem. )

Consequence

BTK
NM_000061.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.961

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-101362230-A-G is Benign according to our data. Variant chrX-101362230-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 530949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.961 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00681 (765/112270) while in subpopulation AFR AF= 0.023 (712/30918). AF 95% confidence interval is 0.0216. There are 7 homozygotes in gnomad4. There are 218 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BTK	NM_000061.3 linkuse as main transcript	c.531T>C	p.Pro177=	synonymous_variant	7/19	ENST00000308731.8	NP_000052.1
BTK	NM_001287344.2 linkuse as main transcript	c.633T>C	p.Pro211=	synonymous_variant	7/19		NP_001274273.1
BTK	NM_001287345.2 linkuse as main transcript	c.531T>C	p.Pro177=	synonymous_variant	8/17		NP_001274274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTK	ENST00000308731.8 linkuse as main transcript	c.531T>C	p.Pro177=	synonymous_variant	7/19	1	NM_000061.3	ENSP00000308176	P3	Q06187-1

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

764

AN:

112215

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

218

AN XY:

34387

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00424

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.00185

AC:

339

AN:

183460

Hom.:

AF XY:

0.00134

AC XY:

AN XY:

67894

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.000668

AC:

733

AN:

1097994

Hom.:

Cov.:

AF XY:

0.000589

AC XY:

214

AN XY:

363348

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00681

AC:

765

AN:

112270

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

218

AN XY:

34452

show subpopulations

Gnomad4 AFR

AF:

0.0230

Gnomad4 AMR

AF:

0.00423

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.00855

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Nov 12, 2021

- -

BTK-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

X-linked agammaglobulinemia with growth hormone deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.79

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