rs2239460

Positions:

• chrX-101384230-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000061.3(BTK):​c.-31+1832C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 111,774 control chromosomes in the GnomAD database, including 296 homozygotes. There are 2,497 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (296 hom., 2497 hem., cov: 23)
• Consequence: BTK NM_000061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTK	NM_000061.3	c.-31+1832C>G		intron_variant		ENST00000308731.8	NP_000052.1
BTK	NM_001287344.2	c.72+6248C>G		intron_variant			NP_001274273.1
BTK	NM_001287345.2	c.-196+1832C>G		intron_variant			NP_001274274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTK	ENST00000308731.8	c.-31+1832C>G		intron_variant		1	NM_000061.3	ENSP00000308176.8

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 8734 AN: 111720 Hom.: 295 Cov.: 23 AF XY: 0.0735 AC XY: 2494 AN XY: 33924

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0206

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0797

Gnomad EAS AF: 0.0365

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0879

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0781 AC: 8735 AN: 111774 Hom.: 296 Cov.: 23 AF XY: 0.0735 AC XY: 2497 AN XY: 33990

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.0797

Gnomad4 EAS AF: 0.0366

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0180 Hom.: 87

Bravo AF: 0.0837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.75
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs2239460; hg19: chrX-100639218;