X-15511457-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_203281.3(BMX):c.264T>A(p.Leu88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,203,289 control chromosomes in the GnomAD database, including 2 homozygotes. There are 746 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., 33 hem., cov: 23)
  • Exomes 𝑓: 0.0019 (2 hom. 713 hem.)
• Consequence: BMX NM_203281.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant X-15511457-T-A is Benign according to our data. Variant chrX-15511457-T-A is described in ClinVar as [Benign]. Clinvar id is 726139.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-15511457-T-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMX	NM_203281.3	c.264T>A	p.Leu88=	synonymous_variant	4/19	ENST00000348343.11
BMX	NM_001721.7	c.264T>A	p.Leu88=	synonymous_variant	4/19
BMX	NM_001320866.2	c.264T>A	p.Leu88=	synonymous_variant	4/19
BMX	XM_017029752.3	c.264T>A	p.Leu88=	synonymous_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMX	ENST00000348343.11	c.264T>A	p.Leu88=	synonymous_variant	4/19	1	NM_203281.3	P1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 121 AN: 111587 Hom.: 0 Cov.: 23 AF XY: 0.000976 AC XY: 33 AN XY: 33801

Gnomad AFR AF: 0.000196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00671

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00131 AC: 233 AN: 178082 Hom.: 1 AF XY: 0.00143 AC XY: 90 AN XY: 63044

Gnomad AFR exome AF: 0.000233

Gnomad AMR exome AF: 0.000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000735

Gnomad SAS exome AF: 0.00491

Gnomad FIN exome AF: 0.000126

Gnomad NFE exome AF: 0.00159

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00185 AC: 2023 AN: 1091649 Hom.: 2 Cov.: 28 AF XY: 0.00199 AC XY: 713 AN XY: 358231

Gnomad4 AFR exome AF: 0.000229

Gnomad4 AMR exome AF: 0.000460

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00637

Gnomad4 FIN exome AF: 0.000173

Gnomad4 NFE exome AF: 0.00183

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.00108 AC: 121 AN: 111640 Hom.: 0 Cov.: 23 AF XY: 0.000974 AC XY: 33 AN XY: 33864

Gnomad4 AFR AF: 0.000195

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00673

Gnomad4 FIN AF: 0.000166

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00113 Hom.: 8

Bravo AF: 0.00108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	8.2
Dann	Benign	0.82

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: rs141827642; hg19: chrX-15529580;