X-15534441-T-G

Variant names:

• chrX-15534441-T-G
• rs1877752
• NM_203281.3:c.1147+102T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203281.3(BMX):​c.1147+102T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 707,813 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000014 (0 hom. 1 hem.)
• Consequence: BMX NM_203281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMX	NM_203281.3	MANE Select	c.1147+102T>G		intron	N/A	NP_975010.1	P51813
	ACE2	NM_001386259.1		c.2310-15462A>C		intron	N/A	NP_001373188.1	A0A7I2V4H0
	BMX	NM_001721.7		c.1147+102T>G		intron	N/A	NP_001712.1	P51813

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMX	ENST00000348343.11	TSL:1 MANE Select	c.1147+102T>G		intron	N/A	ENSP00000308774.6	P51813
	BMX	ENST00000342014.6	TSL:1	c.1147+102T>G		intron	N/A	ENSP00000340082.6	P51813
	ACE2	ENST00000679162.1		c.2309+29583A>C		intron	N/A	ENSP00000503771.1	A0A7I2V3X6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000141 AC: 1 AN: 707813 Hom.: 0 AF XY: 0.00000566 AC XY: 1 AN XY: 176617

African (AFR) AF: 0.00 AC: 0 AN: 15563

American (AMR) AF: 0.00 AC: 0 AN: 12107

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10140

East Asian (EAS) AF: 0.00 AC: 0 AN: 21860

South Asian (SAS) AF: 0.00 AC: 0 AN: 15494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2854

European-Non Finnish (NFE) AF: 0.00000175 AC: 1 AN: 570203

Other (OTH) AF: 0.00 AC: 0 AN: 29790

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.52
DANN	Benign	0.75
PhyloP100		0.22

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

Other links and lift over

dbSNP: rs1877752; hg19: chrX-15552564;