rs1877752

Positions:

• chrX-15534441-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_203281.3(BMX):​c.1147+102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.60 (14355 hom., 19385 hem., cov: 22)
  • Exomes 𝑓: 0.65 (109523 hom. 122280 hem.)
  • Failed GnomAD Quality Control
• Consequence: BMX NM_203281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMX	NM_203281.3	c.1147+102T>C		intron_variant		ENST00000348343.11	NP_975010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMX	ENST00000348343.11	c.1147+102T>C		intron_variant		1	NM_203281.3	ENSP00000308774	P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 65534 AN: 109437 Hom.: 14348 Cov.: 22 AF XY: 0.609 AC XY: 19369 AN XY: 31805

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.556

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.619

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.652 AC: 460211 AN: 706297 Hom.: 109523 AF XY: 0.693 AC XY: 122280 AN XY: 176493

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.599 AC: 65558 AN: 109479 Hom.: 14355 Cov.: 22 AF XY: 0.609 AC XY: 19385 AN XY: 31857

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.623

Alfa AF: 0.609 Hom.: 7262

Bravo AF: 0.604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.57
DANN	Benign	0.77

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: rs1877752; hg19: chrX-15552564; COSMIC: COSV59592747;