X-15534441-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 3 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 -4 ACMG points.

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

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>C		intron	N/A	NP_975010.1	P51813
	ACE2	NM_001386259.1		c.2310-15462A>G		intron	N/A	NP_001373188.1	A0A7I2V4H0
	BMX	NM_001721.7		c.1147+102T>C		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>C		intron	N/A	ENSP00000308774.6	P51813
	BMX	ENST00000342014.6	TSL:1	c.1147+102T>C		intron	N/A	ENSP00000340082.6	P51813
	ACE2	ENST00000679162.1		c.2309+29583A>G		intron	N/A	ENSP00000503771.1	A0A7I2V3X6

Frequencies

GnomAD3 genomes AF: 0.599 AC: 65534 AN: 109437 Hom.: 14348 Cov.: 22

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

African (AFR) AF: 0.447 AC: 6945 AN: 15526

American (AMR) AF: 0.786 AC: 9502 AN: 12086

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 5909 AN: 10122

East Asian (EAS) AF: 0.989 AC: 21622 AN: 21857

South Asian (SAS) AF: 0.733 AC: 11325 AN: 15455

European-Finnish (FIN) AF: 0.699 AC: 20812 AN: 29782

Middle Eastern (MID) AF: 0.568 AC: 1619 AN: 2850

European-Non Finnish (NFE) AF: 0.639 AC: 363333 AN: 568878

Other (OTH) AF: 0.644 AC: 19144 AN: 29741

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

African (AFR) AF: 0.443 AC: 13363 AN: 30193

American (AMR) AF: 0.731 AC: 7446 AN: 10188

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 1523 AN: 2617

East Asian (EAS) AF: 0.984 AC: 3417 AN: 3473

South Asian (SAS) AF: 0.720 AC: 1858 AN: 2582

European-Finnish (FIN) AF: 0.682 AC: 3829 AN: 5613

Middle Eastern (MID) AF: 0.566 AC: 120 AN: 212

European-Non Finnish (NFE) AF: 0.623 AC: 32689 AN: 52444

Other (OTH) AF: 0.623 AC: 931 AN: 1495

Alfa AF: 0.609 Hom.: 7262

Bravo AF: 0.604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.57
DANN	Benign	0.77
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV59592747;