rs16997078

Variant names:

• chrX-15546689-A-G
• rs16997078
• NM_203281.3:c.1677-114A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203281.3(BMX):​c.1677-114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 544,673 control chromosomes in the GnomAD database, including 905 homozygotes. There are 3,997 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 0.068 (608 hom., 2121 hem., cov: 23)
  • Exomes 𝑓: 0.014 (297 hom. 1876 hem.)
• Consequence: BMX NM_203281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

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.1677-114A>G		intron	N/A	NP_975010.1	P51813
	ACE2	NM_001386259.1		c.2309+17335T>C		intron	N/A	NP_001373188.1	A0A7I2V4H0
	BMX	NM_001721.7		c.1677-114A>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.1677-114A>G		intron	N/A	ENSP00000308774.6	P51813
	BMX	ENST00000342014.6	TSL:1	c.1677-114A>G		intron	N/A	ENSP00000340082.6	P51813
	ACE2	ENST00000679162.1		c.2309+17335T>C		intron	N/A	ENSP00000503771.1	A0A7I2V3X6

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 7539 AN: 111734 Hom.: 609 Cov.: 23

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.000164

Gnomad MID AF: 0.0252

Gnomad NFE AF: 0.000751

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0142 AC: 6130 AN: 432882 Hom.: 297 AF XY: 0.0154 AC XY: 1876 AN XY: 121746

African (AFR) AF: 0.226 AC: 2643 AN: 11684

American (AMR) AF: 0.0158 AC: 314 AN: 19863

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10795

East Asian (EAS) AF: 0.0369 AC: 900 AN: 24378

South Asian (SAS) AF: 0.0565 AC: 1428 AN: 25258

European-Finnish (FIN) AF: 0.000289 AC: 10 AN: 34586

Middle Eastern (MID) AF: 0.0215 AC: 44 AN: 2048

European-Non Finnish (NFE) AF: 0.000739 AC: 208 AN: 281483

Other (OTH) AF: 0.0256 AC: 583 AN: 22787

GnomAD4 genome AF: 0.0676 AC: 7552 AN: 111791 Hom.: 608 Cov.: 23 AF XY: 0.0624 AC XY: 2121 AN XY: 33983

African (AFR) AF: 0.224 AC: 6859 AN: 30581

American (AMR) AF: 0.0264 AC: 279 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.0313 AC: 112 AN: 3580

South Asian (SAS) AF: 0.0629 AC: 168 AN: 2672

European-Finnish (FIN) AF: 0.000164 AC: 1 AN: 6084

Middle Eastern (MID) AF: 0.0276 AC: 6 AN: 217

European-Non Finnish (NFE) AF: 0.000751 AC: 40 AN: 53236

Other (OTH) AF: 0.0572 AC: 87 AN: 1521

Alfa AF: 0.0514 Hom.: 191

Bravo AF: 0.0763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.75
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16997078; hg19: chrX-15564812;