Variant rs128621199 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000061.3(BTK):c.1275C>T(p.Tyr425Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,209,594 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000023 ( 0 hom. 5 hem. )

Consequence

BTK
NM_000061.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.546

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:

BTK (HGNC:):

BTK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-101356858-G-A is Benign according to our data. Variant chrX-101356858-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2418367.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.546 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000228 (25/1098001) while in subpopulation EAS AF= 0.000695 (21/30204). AF 95% confidence interval is 0.000465. There are 0 homozygotes in gnomad4_exome. There are 5 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTK	NM_000061.3 linkuse as main transcript	c.1275C>T	p.Tyr425Tyr	synonymous_variant	14/19	ENST00000308731.8	NP_000052.1	Q06187-1Q5JY90
BTK	NM_001287344.2 linkuse as main transcript	c.1377C>T	p.Tyr459Tyr	synonymous_variant	14/19		NP_001274273.1	Q06187-2
BTK	NM_001287345.2 linkuse as main transcript	c.1038+1516C>T		intron_variant			NP_001274274.1	Q06187Q5JY90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTK	ENST00000308731.8 linkuse as main transcript	c.1275C>T	p.Tyr425Tyr	synonymous_variant	14/19	1	NM_000061.3	ENSP00000308176.8		Q06187-1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111593

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33773

show subpopulations

Gnomad AFR

AF:

0.0000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183502

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67940

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1098001

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363357

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000695

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111593

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33773

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked agammaglobulinemia with growth hormone deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.7

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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