rs35697037

Variant names:

• chrX-15523993-G-A
• rs35697037
• NM_203281.3:c.753-1295G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-15523993-G-A
• chrX-15523993-G-T

Variant summary

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

The NM_203281.3(BMX):​c.753-1295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 111,062 control chromosomes in the GnomAD database, including 5,456 homozygotes. There are 12,183 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 0.37 (5456 hom., 12183 hem., cov: 23)
• Consequence: BMX NM_203281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.994
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMX	NM_203281.3	c.753-1295G>A		intron_variant	Intron 7 of 18	ENST00000348343.11	NP_975010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMX	ENST00000348343.11	c.753-1295G>A		intron_variant	Intron 7 of 18	1	NM_203281.3	ENSP00000308774.6

Frequencies

GnomAD3 genomes AF: 0.367 AC: 40705 AN: 111011 Hom.: 5457 Cov.: 23

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 40721 AN: 111062 Hom.: 5456 Cov.: 23 AF XY: 0.366 AC XY: 12183 AN XY: 33314

African (AFR) AF: 0.277 AC: 8469 AN: 30629

American (AMR) AF: 0.359 AC: 3785 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 929 AN: 2631

East Asian (EAS) AF: 0.431 AC: 1509 AN: 3503

South Asian (SAS) AF: 0.255 AC: 688 AN: 2693

European-Finnish (FIN) AF: 0.501 AC: 2916 AN: 5819

Middle Eastern (MID) AF: 0.361 AC: 78 AN: 216

European-Non Finnish (NFE) AF: 0.408 AC: 21548 AN: 52846

Other (OTH) AF: 0.361 AC: 548 AN: 1518

Alfa AF: 0.391 Hom.: 4340

Bravo AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.71
PhyloP100		0.99
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: rs35697037; hg19: chrX-15542116;