rs35697037

chrX-15523993-G-AchrX-15523993-G-T

Variant summary

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

The NM_203281.3(BMX):c.753-1295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 111,062 control chromosomes in the GnomAD database, including 5,456 homozygotes. There are 12,183 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 0.37 (5456 hom., 12183 hem., cov: 23)
• Consequence: BMX NM_203281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.994

Genes affected

BMX (HGNC:1079): (BMX non-receptor tyrosine kinase) This gene encodes a non-receptor tyrosine kinase belonging to the Tec kinase family. The protein contains a PH-like domain, which mediates membrane targeting by binding to phosphatidylinositol 3,4,5-triphosphate (PIP3), and a SH2 domain that binds to tyrosine-phosphorylated proteins and functions in signal transduction. The protein is implicated in several signal transduction pathways including the Stat pathway, and regulates differentiation and tumorigenicity of several types of cancer cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ACE2 (HGNC:13557): (angiotensin converting enzyme 2) The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMX	NM_203281.3	c.753-1295G>A		intron_variant		ENST00000348343.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMX	ENST00000348343.11	c.753-1295G>A		intron_variant		1	NM_203281.3	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 40705 AN: 111011 Hom.: 5457 Cov.: 23 AF XY: 0.366 AC XY: 12168 AN XY: 33253

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.367 AC: 40721 AN: 111062 Hom.: 5456 Cov.: 23 AF XY: 0.366 AC XY: 12183 AN XY: 33314

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.361

Alfa AF: 0.391 Hom.: 4340

Bravo AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.71

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: rs35697037; hg19: chrX-15542116;